[Source: TGen] - The Translational Genomics Research Institute (TGen) and the Van Andel Research Institute (VARI) will forge a strategic alliance that will enable both to maximize their worldwide contributions to science and health.
The non-profit researcher institutes jointly announced today the initiation of an "alliance and affiliation agreement."
The partnership between Phoenix, Ariz.-based TGen and Grand Rapids, Mich.-based VARI will enable both institutes to speed up their mutual goals of moving research discoveries about cancer and other debilitating medical conditions as quickly as possible from laboratories to patient care.
"Combining many of the scientific, educational, financial and business potentials of TGen and VARI will advance the research of both institutions and enhance the economic development of both Arizona and Western Michigan," said Dr. Jeffrey Trent, President and Scientific Director of TGen since its founding in 2002.
"This alliance will elevate both organizations in the world of scientific research," said Dr. Trent, who will retain his roles at TGen, but upon implementation of the agreement also will become President and Research Director of VARI.
VARI is the research arm of the Van Andel Institute (VAI), established in 1996 as a philanthropic research and educational organization by the late Jay and Betty Van Andel.
"We are excited to welcome Dr. Trent and TGen as they combine forces with us in our mission to conquer cancer and human disease," said VAI Chairman and CEO David Van Andel. "This alliance demonstrates that VARI and TGen are at the forefront of redefining a borderless, collaborative, national and international scientific community that transcends geographical limitations."
The alliance combines the groundbreaking basic research expertise of VARI with the cutting-edge translational genomics and analysis of TGen.
Dr. Trent will replace Dr. George Vande Woude, who in 1998 was appointed the founding Director of VARI.
"The search for a new director has ended with the best possible results - a renowned, research director in Dr. Trent, who will now lead VARI, and an alliance that strengthens two of the nation's fast-emerging leaders in biomedical research," David Van Andel said.
Dr. Vande Woude, a member of the prestigious National Academy of Sciences, will remain at VARI as head of the Laboratory of Molecular Oncology. Dr. Vande Woude, who held top-level administrative posts at the National Cancer Institute since the early 1980's, will be able to achieve a long-held desire to return to the lab full-time.
"This is a great moment for both Institutions. I have known Dr.Trent professionally for nearly 20 years and have always admired him as one of the nation's leading scientists. One of Dr. Trent's greatest attributes is bringing together researchers from many disciplines to work on problems that will improve human health," Dr. Vande Woude said.
TGen is dedicated to conducting groundbreaking research with life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders, diabetes and infectious diseases. TGen is on the cutting edge of translational research, in which investigators unravel the genetic basis of complex diseases and medical conditions.
VARI opened its facility in 2000. Its 18 research laboratories are primarily dedicated to molecular cancer research, but it also focuses on conditions such as diabetes, Parkinson's disease, osteoporosis, and heart disease. VARI will open a 240,000 square-foot building expansion this fall, which will allow it to broaden its efforts to include additional neurological disorders and chronic illnesses. VARI's primary work has been in basic research - looking for what occurs to cause disease in individual cells, and using that information to identify "biomarkers" that can help predict and diagnose diseases, and lead to the development of safer, more effective drugs.
"VARI is on the verge of expanding its already strong basic research programs and implementing further translational research," said Dr. Daniel Von Hoff, TGen's Physician-In-Chief and a world-renowned cancer scientist.
"TGen is poised to translate the discoveries generated in laboratories from both organizations into real solutions for patients," said Dr. Von Hoff, who also is Chief Scientific Officer of TGen Clinical Research Services at Scottsdale Healthcare. "This is a terrific opportunity to work together and increase our chances of making a difference for our patients."
Both TGen and VARI are relatively young organizations that have triggered regional growth of the life sciences and biomedical industries in Arizona and Western Michigan.
Both organizations have a strong focus on cancer, collaborations and expansion locally, nationally and internationally.
The "alliance and affiliation agreement" is expected to become effective July 1, 2009.
Showing posts with label Neuroscience. Show all posts
Showing posts with label Neuroscience. Show all posts
Wednesday, February 11, 2009
Monday, January 5, 2009
Blind man "sees," cruising through obstacle course without a hitch
[Source Scientific American, Coco Ballantyne ] - A man left totally blind by a massive stroke navigated a complex maze of boxes, chairs and other objects without stumbling or colliding into any of the obstacles.
Brain scans showed that after suffering two consecutive strokes, the man, 56, lost all function in his visual cortex, the brain's primary vision-processing center. But despite the loss, an international research team (from the U.S. and five other countries) reports in the journal Current Biology that "he could successfully navigate down the extent of a long corridor in which various barriers were placed."
Neuroscientists call this ability blindsight. People with blindsight, "usually tell you that they cannot see a thing…. They cannot consciously see but they have some type of awareness," says Susana Martinez-Conde, a neuroscientist at the Barrow Neurological Institute in Phoenix, Ariz. For instance, she notes, they will correctly guess the number on flashcards more than 50 percent of the time even though their eyesight is shot.
In a person with normal vision, information is passed from the retina (light sensitive area at the back of the eyes) to the visual cortex (the brain's vision center), which relays it to other brain processing areas such as the posterior parietal cortex. In this man's case, the retinas worked perfectly well, but the information highway to the brain was blocked at the visual cortex.
This means that the man must have been using alternative pathways (that bypassed the visual cortex) to connect to the other brain processing regions, Martinez-Conde says, noting that most people likely have these alternate routes but don't rely on them because the dominant visual cortex pathway functions properly.
This study is not the first to document blightsightness, but it is first to describe the phenomenon in a patient who had suffered destruction of the visual cortex in both hemispheres of the brain, according to Nature News.
Over the past several years, scientists have identified brain circuits that may serve as alternative routes, but have yet to pinpoint which ones enable blindsightness, and exactly how they function. But Martinez-Conde says that a combo of electroencephalography (EEG), which measures electrical activity in the brain over time, and functional magnetic resonance imaging (fMRI), which shows blood flow to areas of the brain that are active, may shed light on these circuits.
Brain scans showed that after suffering two consecutive strokes, the man, 56, lost all function in his visual cortex, the brain's primary vision-processing center. But despite the loss, an international research team (from the U.S. and five other countries) reports in the journal Current Biology that "he could successfully navigate down the extent of a long corridor in which various barriers were placed."
Neuroscientists call this ability blindsight. People with blindsight, "usually tell you that they cannot see a thing…. They cannot consciously see but they have some type of awareness," says Susana Martinez-Conde, a neuroscientist at the Barrow Neurological Institute in Phoenix, Ariz. For instance, she notes, they will correctly guess the number on flashcards more than 50 percent of the time even though their eyesight is shot.
In a person with normal vision, information is passed from the retina (light sensitive area at the back of the eyes) to the visual cortex (the brain's vision center), which relays it to other brain processing areas such as the posterior parietal cortex. In this man's case, the retinas worked perfectly well, but the information highway to the brain was blocked at the visual cortex.
This means that the man must have been using alternative pathways (that bypassed the visual cortex) to connect to the other brain processing regions, Martinez-Conde says, noting that most people likely have these alternate routes but don't rely on them because the dominant visual cortex pathway functions properly.
This study is not the first to document blightsightness, but it is first to describe the phenomenon in a patient who had suffered destruction of the visual cortex in both hemispheres of the brain, according to Nature News.
Over the past several years, scientists have identified brain circuits that may serve as alternative routes, but have yet to pinpoint which ones enable blindsightness, and exactly how they function. But Martinez-Conde says that a combo of electroencephalography (EEG), which measures electrical activity in the brain over time, and functional magnetic resonance imaging (fMRI), which shows blood flow to areas of the brain that are active, may shed light on these circuits.
Thursday, December 11, 2008
ASU study aims to fight symptoms of Parkinson's
[Source: Scott Huscher, ASUWebDevil] - Although many wouldn’t think ski poles could fight the symptoms of Parkinson’s disease (PD), a new Arizona State University study is trying to prove just that.
“Exercise training in Parkinson’s disease: Neural and functional benefits” aims to see if exercise is a key component in decreasing the symptoms of PD. The study will utilize “polestriding,” which is walking with the aid of ski-like poles. Also known as Nordic walking, the poles will help with balance, which many people with PD have trouble with.
“PD is a progressive disease in which the cells in an area of the brain called the substantia nigra that produce the neurotransmitter called dopamine keep dying,” said Narayanan Krishnamurthi, principal investigator for the study and assistant professor of research at ASU’s Center for Adaptive Neural Systems in the Ira A. Fulton School of Engineering. “So if exercise can protect neurons or it can create new neurons it’s a good possibility that the progression of the disease can be stopped or reversed.”
Krishnamurthi said that he was motivated to do the study based on previous reports that animals with PD-like symptoms benefited from exercise.
“The animals that participated in the exercise program had less severe symptoms and didn’t lose as many neurons as the animals that didn’t participate in the exercise.” Krishnamurthi said.
Krishnamurthi said that other studies have shown that people with higher cardiac and aerobic fitness have better brain health than those who do not regularly exercise.
“This study investigates the functional benefits with respect to motor and non-motor symptoms before and after the exercise training for 12 weeks,” Krishnamurthi said.
This study, which was recently funded by the National Institutes of Health, is a collaborative effort between the Center for Adaptive Neural Systems at ASU, the Muhammad Ali Parkinson Center at the Barrow Neurological Institute, the PET Imaging Center at the Banner Alzheimer’s Institute, and the Christopher Center for Parkinson’s Research at Sun Health Research Institute.
It will involve sixteen participants with PD between the ages of 50-70, because PD usually has its onset after the age of 50.
Each participant will be involved in a 36-week period in which half of the participants will receive PET scans before and after the exercise period to see if there are any positive changes in their brain glucose consumption. The PET scans will be conducted at the Banner Alzheimer’s Institute.
“We’ll see if the exercise training produces changes in the brain metabolic activity patterns from abnormal patterns specific to PD towards the patterns of healthy people,” Krishnamurthi said. “That will give us an indication whether exercise is capable of improving brain health in PD.”
The functional outcome measurements will be completed at the Sun Health Research Institute in Sun City. The exercise sessions will be conducted by Darolyn O’Donnell, recreation therapy coordinator at the Muhammad Ali Parkinson Center at the Barrow Neurological Institute.
“What we aim to do is establish and provide exercise therapy people can do on their own,” O’Donnell said.
The initial idea to use poles came from a personal experience. James Abbas, a co-investigator on the study and co-director of the Center for Adaptive Neural Systems at ASU, learned about how the use of poles can increase the intensity of walking exercise and observed how they helped his mother feel more secure while walking. Since previous research results suggested an important role for exercise and clinical experience pointed to the need for some assistance during walking, the team decided to go forward with the study.
O’Donnell also said that the polestriding was chosen because it provides balance, helps work the upper body and targets core muscle. It’s also more aerobic than normal walking.
The exercise will last 45 minutes to an hour, three times per week.
Right now, the study is still in its initial phases, setting up software and hardware and recruiting participants for the study. Krishnamurthi said they should begin data collection with the first group of participants either this February or March.
“If it is really beneficial, it will be very helpful to alleviate the symptoms since current treatments do not provide cure and are generally ineffective during advanced stages of the disease,” Krishnamurthi said.
If the exercise helps fight against symptoms of PD, he said it will help those with PD everywhere.
“Since exercise can be done in any part of the world, people in underdeveloped countries where medical treatment for diseases like PD is not easily affordable can also benefit significantly.”
“Exercise training in Parkinson’s disease: Neural and functional benefits” aims to see if exercise is a key component in decreasing the symptoms of PD. The study will utilize “polestriding,” which is walking with the aid of ski-like poles. Also known as Nordic walking, the poles will help with balance, which many people with PD have trouble with.
“PD is a progressive disease in which the cells in an area of the brain called the substantia nigra that produce the neurotransmitter called dopamine keep dying,” said Narayanan Krishnamurthi, principal investigator for the study and assistant professor of research at ASU’s Center for Adaptive Neural Systems in the Ira A. Fulton School of Engineering. “So if exercise can protect neurons or it can create new neurons it’s a good possibility that the progression of the disease can be stopped or reversed.”
Krishnamurthi said that he was motivated to do the study based on previous reports that animals with PD-like symptoms benefited from exercise.
“The animals that participated in the exercise program had less severe symptoms and didn’t lose as many neurons as the animals that didn’t participate in the exercise.” Krishnamurthi said.
Krishnamurthi said that other studies have shown that people with higher cardiac and aerobic fitness have better brain health than those who do not regularly exercise.
“This study investigates the functional benefits with respect to motor and non-motor symptoms before and after the exercise training for 12 weeks,” Krishnamurthi said.
This study, which was recently funded by the National Institutes of Health, is a collaborative effort between the Center for Adaptive Neural Systems at ASU, the Muhammad Ali Parkinson Center at the Barrow Neurological Institute, the PET Imaging Center at the Banner Alzheimer’s Institute, and the Christopher Center for Parkinson’s Research at Sun Health Research Institute.
It will involve sixteen participants with PD between the ages of 50-70, because PD usually has its onset after the age of 50.
Each participant will be involved in a 36-week period in which half of the participants will receive PET scans before and after the exercise period to see if there are any positive changes in their brain glucose consumption. The PET scans will be conducted at the Banner Alzheimer’s Institute.
“We’ll see if the exercise training produces changes in the brain metabolic activity patterns from abnormal patterns specific to PD towards the patterns of healthy people,” Krishnamurthi said. “That will give us an indication whether exercise is capable of improving brain health in PD.”
The functional outcome measurements will be completed at the Sun Health Research Institute in Sun City. The exercise sessions will be conducted by Darolyn O’Donnell, recreation therapy coordinator at the Muhammad Ali Parkinson Center at the Barrow Neurological Institute.
“What we aim to do is establish and provide exercise therapy people can do on their own,” O’Donnell said.
The initial idea to use poles came from a personal experience. James Abbas, a co-investigator on the study and co-director of the Center for Adaptive Neural Systems at ASU, learned about how the use of poles can increase the intensity of walking exercise and observed how they helped his mother feel more secure while walking. Since previous research results suggested an important role for exercise and clinical experience pointed to the need for some assistance during walking, the team decided to go forward with the study.
O’Donnell also said that the polestriding was chosen because it provides balance, helps work the upper body and targets core muscle. It’s also more aerobic than normal walking.
The exercise will last 45 minutes to an hour, three times per week.
Right now, the study is still in its initial phases, setting up software and hardware and recruiting participants for the study. Krishnamurthi said they should begin data collection with the first group of participants either this February or March.
“If it is really beneficial, it will be very helpful to alleviate the symptoms since current treatments do not provide cure and are generally ineffective during advanced stages of the disease,” Krishnamurthi said.
If the exercise helps fight against symptoms of PD, he said it will help those with PD everywhere.
“Since exercise can be done in any part of the world, people in underdeveloped countries where medical treatment for diseases like PD is not easily affordable can also benefit significantly.”
Tuesday, December 9, 2008
Understanding Brain Tumor Growth Through Applying Weather Forecasting Technology
[Source: ScienceDaily] - Researchers and students from St. Joseph's Hospital and Medical Center and Arizona State University's Math Department are applying weather forecast technology to model and track the growth patterns of brain tumors.
The technology allows researchers to study various growth patterns of brain tumors and apply treatment parameters to determine the best option for patients. It will forecast how a patient's tumor may grow with different treatment scenarios, help physicians make a much more informed prognosis and be used as a patient consulting tool.
The research study began when Barrow and ASU researchers Mark Preul, Yang Kuang and Eric Kostelich used data from a collection of normal brain images to create a life-like recreation of the brain. They positioned a virtual tumor in the brain image and applied intricate math formulas used in weather forecast technology to predict how the tumor would grow.
Once the virtual tumor began to grow, the researchers determined a way to resect part of the tumor and gave it the effects of radiation and chemotherapy to see how the tumor would respond. A patient study was eventually used to compare the tumor growth and outcome between the patient and virtual model. They closely matched.
"This study has resulted in the most accurate and life-like recreation of the growth of malignant brain tumors," says Mark Preul, MD, Newsome Chair of Neurosurgery Research. "The technology used in the study could pave the way for better treatment plans enabling a greater outcome for patients,"
The study will be published in Cell Proliferation and is the basis for a National Science Foundation grant submission. The Barrow Neurological Foundation funded the initial study.
The technology allows researchers to study various growth patterns of brain tumors and apply treatment parameters to determine the best option for patients. It will forecast how a patient's tumor may grow with different treatment scenarios, help physicians make a much more informed prognosis and be used as a patient consulting tool.
The research study began when Barrow and ASU researchers Mark Preul, Yang Kuang and Eric Kostelich used data from a collection of normal brain images to create a life-like recreation of the brain. They positioned a virtual tumor in the brain image and applied intricate math formulas used in weather forecast technology to predict how the tumor would grow.
Once the virtual tumor began to grow, the researchers determined a way to resect part of the tumor and gave it the effects of radiation and chemotherapy to see how the tumor would respond. A patient study was eventually used to compare the tumor growth and outcome between the patient and virtual model. They closely matched.
"This study has resulted in the most accurate and life-like recreation of the growth of malignant brain tumors," says Mark Preul, MD, Newsome Chair of Neurosurgery Research. "The technology used in the study could pave the way for better treatment plans enabling a greater outcome for patients,"
The study will be published in Cell Proliferation and is the basis for a National Science Foundation grant submission. The Barrow Neurological Foundation funded the initial study.
Monday, December 8, 2008
Sun Health launches Parkinson's study
[Source: AzCentral.com] - The Michael J. Fox Foundation has awarded the Sun Health Research Institute a $75,000 grant to study new equipment that treats Parkinson's disease, adding to the growing list of activities at the Northwest Valley research facility.
The Parkinson's study is the institute's first major undertaking since it was acquired by Banner Health in September. The merger gave the institute a larger talent pool of scientists for such studies, since it now has access to resources at the Banner Alzheimer's Institute, a research facility in Phoenix.
The growth in local medical research doesn't only mean access to top-notch care for local residents. It is another piece in the economic-development puzzle for Surprise, the Sun Cities and other area communities, improving their prospects for attracting high-paying jobs in the fields of health and sciences.
"It just sort of shows there's activity going on here, and it plays into our overall strategy in trying to create some jobs in the whole medical arena, whether it's health care or research and development," Surprise Economic Development Director John Hagen said.
The new Parkinson's study examines the use of Nexalin headgear, a pad that attaches to patients' forehead. Electrodes connected to the pad emit low-frequency triggers that are supposed to stop Parkinson's tremors. The treatments are administered one hour a day, five days a week, for two weeks during the study.
What has researchers excited is Nexalin's "no fuss, no muss" appeal. Surgery is not required for the treatment.
"The procedure is non-invasive because it's actually headgear that you wear. It would be invasive if it went inside your body," said Banner Health spokeswoman Elle Shelley.
The Institute has six participants for the study, and a goal of getting 18 more.
Since opening its clinical-trial program eight years ago, Sun Health has conducted a variety of studies, and the Parkinson's trial is just one of a handful currently getting underway, according to Brian Browne, the Research Institute's public information officer. Eleven clinical studies are preparing to enroll participants, he said.
Most of Sun Health's trials involve those afflicted with Parkinson's and Alzheimer's diseases, though one underway is a bladder-cancer clinical trial.
Browne said the Valley, particularly retirement areas like the Sun Cities, are prime targets for such clinical studies because it is in these communities "where we are seeing a number of neurological degenerative diseases of aging."
Browne said the recent merger of Banner and Sun Health "has positively impacted the way we do clinical trials. Some of our clinical trials are done in conjunction with our sister institute, Banner Alzheimer's Institute in Phoenix, and when you have that kind of synergy, you do much more in collaboration than separtely."
Banner's ownership transition, however, will continue to affect Surprise's efforts to get a biotech campus off the ground, Hagen said.
"Until that acquisition is fully digested, they're not going to be as big a player as we like," Hagen said, adding he expects the transition to last another six to 12 months.
Surprise, however, continues to pursue other medical and biotechnology opportunities.
The city recently announced that three science-related firms are interested in leasing the old City Hall building on Bell Road to serve as an incubator for start-up companies. City leaders are weighing each option, and a decision eventually will go before the City Council.
The city will not elaborate on the proposals until discussions proceed, Hagen said.
The city also has identified several key land parcels with potential for biotech development. It has put the most emphasis on 500-plus acres south of Bell Road and Bullard Avenue that is expected to become the future downtown. Sun Health Properties, a land-ownership group separate from the research institute, has a stake in that property.
There also is land at the city's Southwest Railplex, bordered by Peoria Avenue and Dysart, Waddell and Litchfield roads, and at the Prasada development along Loop 303, Hagen said.
For information on the new Parkinson's clinical trial, call 623-875-6500.
The Parkinson's study is the institute's first major undertaking since it was acquired by Banner Health in September. The merger gave the institute a larger talent pool of scientists for such studies, since it now has access to resources at the Banner Alzheimer's Institute, a research facility in Phoenix.
The growth in local medical research doesn't only mean access to top-notch care for local residents. It is another piece in the economic-development puzzle for Surprise, the Sun Cities and other area communities, improving their prospects for attracting high-paying jobs in the fields of health and sciences.
"It just sort of shows there's activity going on here, and it plays into our overall strategy in trying to create some jobs in the whole medical arena, whether it's health care or research and development," Surprise Economic Development Director John Hagen said.
The new Parkinson's study examines the use of Nexalin headgear, a pad that attaches to patients' forehead. Electrodes connected to the pad emit low-frequency triggers that are supposed to stop Parkinson's tremors. The treatments are administered one hour a day, five days a week, for two weeks during the study.
What has researchers excited is Nexalin's "no fuss, no muss" appeal. Surgery is not required for the treatment.
"The procedure is non-invasive because it's actually headgear that you wear. It would be invasive if it went inside your body," said Banner Health spokeswoman Elle Shelley.
The Institute has six participants for the study, and a goal of getting 18 more.
Since opening its clinical-trial program eight years ago, Sun Health has conducted a variety of studies, and the Parkinson's trial is just one of a handful currently getting underway, according to Brian Browne, the Research Institute's public information officer. Eleven clinical studies are preparing to enroll participants, he said.
Most of Sun Health's trials involve those afflicted with Parkinson's and Alzheimer's diseases, though one underway is a bladder-cancer clinical trial.
Browne said the Valley, particularly retirement areas like the Sun Cities, are prime targets for such clinical studies because it is in these communities "where we are seeing a number of neurological degenerative diseases of aging."
Browne said the recent merger of Banner and Sun Health "has positively impacted the way we do clinical trials. Some of our clinical trials are done in conjunction with our sister institute, Banner Alzheimer's Institute in Phoenix, and when you have that kind of synergy, you do much more in collaboration than separtely."
Banner's ownership transition, however, will continue to affect Surprise's efforts to get a biotech campus off the ground, Hagen said.
"Until that acquisition is fully digested, they're not going to be as big a player as we like," Hagen said, adding he expects the transition to last another six to 12 months.
Surprise, however, continues to pursue other medical and biotechnology opportunities.
The city recently announced that three science-related firms are interested in leasing the old City Hall building on Bell Road to serve as an incubator for start-up companies. City leaders are weighing each option, and a decision eventually will go before the City Council.
The city will not elaborate on the proposals until discussions proceed, Hagen said.
The city also has identified several key land parcels with potential for biotech development. It has put the most emphasis on 500-plus acres south of Bell Road and Bullard Avenue that is expected to become the future downtown. Sun Health Properties, a land-ownership group separate from the research institute, has a stake in that property.
There also is land at the city's Southwest Railplex, bordered by Peoria Avenue and Dysart, Waddell and Litchfield roads, and at the Prasada development along Loop 303, Hagen said.
For information on the new Parkinson's clinical trial, call 623-875-6500.
Friday, December 5, 2008
HIV Dementia: How Major HIV Strains Affect The Brain Differently
[Source: ScienceDaily ] - A new study led by researchers at Albert Einstein College of Medicine of Yeshiva University has clarified how two major variants of HIV differ in their ability to cause neurologic complications. The finding, published in Journal of Neuroscience, highlights a new target for drugs that could prevent HIV-associated dementia, an incurable and increasingly common complication in people with AIDS.
Even with anti-retroviral drug therapies, up to one-half of people infected with HIV will develop mild to moderate neurological complications, according to some estimates.
Earlier this decade, scientists observed that people with AIDS in India developed dementia at a far lower rate than comparable populations in the U.S. and Western Europe. Most cases of AIDS in India are due to infection with a subtype or clade of HIV, known as clade C, while most cases in the U.S. and Western Europe are due to clade B.
Based on these observations, in 2004, a team of researchers led by Dr. Vinayaka R. Prasad, professor of microbiology and immunology at Einstein, began searching for genetic variations between the two clades that could explain the differing rates of HIV-related dementia. The team, in collaboration with Dr. Udaykumar Ranga of the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India, focused their search on Tat, a protein that helps HIV replicate and leads the attack on the brain.
Dr. Prasad and colleagues compared the sequences of the Tat protein of the two clades and noted a key difference. Where the clade B Tat protein contained the amino acid cysteine at a specific position in the Tat protein, the clade C Tat had the amino acid serine. The next step, and the focus of the current study, was to compare the two viruses in a single host to determine whether this key change in the amino acid sequence makes a practical difference in HIV's neurotoxicity.
To find out, the researchers injected either clade B or clade C HIV into the brain of a special strain of immunodeficient mice. After six days--enough time for the viruses to cause neurologic damage--the mice were tested in a complex water maze that challenged their long term memory as well as their short term working memory (the type that temporarily stores and manages the information needed to carry out complex cognitive tasks, such as learning, reasoning, and comprehension).
Mice infected with clade B performed significantly worse in the maze than those infected with clade C. Moreover, when the researchers examined the mouse brains, they found more damage to neurons in the brains of mice injected with clade B than with clade C. These results were in line with the fact that people infected with clade B HIV are at greater risk for dementia than people infected with clade C.
This is the first evidence in an animal model that HIV variants from different parts of the world differ in their ability to cause neurological complications. Further, test tube studies conducted at Einstein showed strain differences in recruiting inflammatory cells to the brain. Thus, these data now provide biological evidence that Tat protein plays a crucial role in the development of HIV-related dementia.
"Tat seems to be responsible for most of the neurological symptoms seen in patients with HIV-associated dementia," says Dr. Prasad. "People have always suspected Tat to be a key protein in HIV dementia based on test tube studies. Credit for that work belongs to, among others, Dr. Joan Berman, also from Einstein. Our results, obtained using live virus in an animal model to compare genetic variants, suggest that a drug that targets HIV-1 Tat might prevent the neurological effects of AIDS."
The need for drugs that prevent HIV-dementia has grown more acute in recent years, notes Dr. Prasad. Thanks to advances in therapy, people with HIV are living increasingly longer. In 1996, a 20-year-old newly diagnosed with HIV could expect to live another 36 years, according to a recent study in The Lancet. Today, that same person could expect to live another 49 years.
However, because anti-retroviral drugs do not fully eradicate HIV from the brain or the rest of the body, the low levels of virus that remain can cause significant damage.
The findings raise a larger issue, say the researchers. There appear to be significant differences between the major strains of HIV, perhaps warranting different therapeutic approaches.
"Roughly 60 percent of the HIV infections worldwide are due to clade C, but all effective therapies are based on clade B," says Dr. Vasudev R. Rao, lead author of the study and research associate in microbiology and immunology at Einstein. "While our findings specifically address the differences between clade B and clade C with regard to the manifestation of HIV-associated dementia, investigating subtype differences has broad implications for clinical management and treatment for the global AIDS epidemic."
In addition to Drs. Prasad and Rao, the research team included Dr. William R. Tyor of the Medical University of South Carolina in Charleston, and a member of his research team, Dr. Andrew R. Sas; Dr. Eliseo A. Eugenin, assistant professor of pathology at Einstein; Dr. Udaykumar Ranga and a member of his laboratory, Dr. Nagadenahalli B. Siddappa of the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India; Dr. Heather Bimonte-Nelson of Arizona State University in Tempe and Dr. Joan W. Berman, professor of pathology, microbiology and immunology at Einstein.
Even with anti-retroviral drug therapies, up to one-half of people infected with HIV will develop mild to moderate neurological complications, according to some estimates.
Earlier this decade, scientists observed that people with AIDS in India developed dementia at a far lower rate than comparable populations in the U.S. and Western Europe. Most cases of AIDS in India are due to infection with a subtype or clade of HIV, known as clade C, while most cases in the U.S. and Western Europe are due to clade B.
Based on these observations, in 2004, a team of researchers led by Dr. Vinayaka R. Prasad, professor of microbiology and immunology at Einstein, began searching for genetic variations between the two clades that could explain the differing rates of HIV-related dementia. The team, in collaboration with Dr. Udaykumar Ranga of the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India, focused their search on Tat, a protein that helps HIV replicate and leads the attack on the brain.
Dr. Prasad and colleagues compared the sequences of the Tat protein of the two clades and noted a key difference. Where the clade B Tat protein contained the amino acid cysteine at a specific position in the Tat protein, the clade C Tat had the amino acid serine. The next step, and the focus of the current study, was to compare the two viruses in a single host to determine whether this key change in the amino acid sequence makes a practical difference in HIV's neurotoxicity.
To find out, the researchers injected either clade B or clade C HIV into the brain of a special strain of immunodeficient mice. After six days--enough time for the viruses to cause neurologic damage--the mice were tested in a complex water maze that challenged their long term memory as well as their short term working memory (the type that temporarily stores and manages the information needed to carry out complex cognitive tasks, such as learning, reasoning, and comprehension).
Mice infected with clade B performed significantly worse in the maze than those infected with clade C. Moreover, when the researchers examined the mouse brains, they found more damage to neurons in the brains of mice injected with clade B than with clade C. These results were in line with the fact that people infected with clade B HIV are at greater risk for dementia than people infected with clade C.
This is the first evidence in an animal model that HIV variants from different parts of the world differ in their ability to cause neurological complications. Further, test tube studies conducted at Einstein showed strain differences in recruiting inflammatory cells to the brain. Thus, these data now provide biological evidence that Tat protein plays a crucial role in the development of HIV-related dementia.
"Tat seems to be responsible for most of the neurological symptoms seen in patients with HIV-associated dementia," says Dr. Prasad. "People have always suspected Tat to be a key protein in HIV dementia based on test tube studies. Credit for that work belongs to, among others, Dr. Joan Berman, also from Einstein. Our results, obtained using live virus in an animal model to compare genetic variants, suggest that a drug that targets HIV-1 Tat might prevent the neurological effects of AIDS."
The need for drugs that prevent HIV-dementia has grown more acute in recent years, notes Dr. Prasad. Thanks to advances in therapy, people with HIV are living increasingly longer. In 1996, a 20-year-old newly diagnosed with HIV could expect to live another 36 years, according to a recent study in The Lancet. Today, that same person could expect to live another 49 years.
However, because anti-retroviral drugs do not fully eradicate HIV from the brain or the rest of the body, the low levels of virus that remain can cause significant damage.
The findings raise a larger issue, say the researchers. There appear to be significant differences between the major strains of HIV, perhaps warranting different therapeutic approaches.
"Roughly 60 percent of the HIV infections worldwide are due to clade C, but all effective therapies are based on clade B," says Dr. Vasudev R. Rao, lead author of the study and research associate in microbiology and immunology at Einstein. "While our findings specifically address the differences between clade B and clade C with regard to the manifestation of HIV-associated dementia, investigating subtype differences has broad implications for clinical management and treatment for the global AIDS epidemic."
In addition to Drs. Prasad and Rao, the research team included Dr. William R. Tyor of the Medical University of South Carolina in Charleston, and a member of his research team, Dr. Andrew R. Sas; Dr. Eliseo A. Eugenin, assistant professor of pathology at Einstein; Dr. Udaykumar Ranga and a member of his laboratory, Dr. Nagadenahalli B. Siddappa of the Jawaharlal Nehru Centre for Advanced Scientific Research in Bangalore, India; Dr. Heather Bimonte-Nelson of Arizona State University in Tempe and Dr. Joan W. Berman, professor of pathology, microbiology and immunology at Einstein.
Tuesday, November 25, 2008
Reliability Of Cognitive Assessment Tool Varies Widely, Study Suggests
[Source: ScienceDaily] - A new suggests the reliability of the Alzheimer's Disease Assessment Scale – Cognitive (ADAS-Cog) may vary and possess the ability to affect clinical trial outcomes.
Moreover, this study further suggests that ADAS-Cog rater training and experience are factors that contribute to variances seen in this assessment tool.
The importance of a reliable diagnosis of the Alzheimer's disease (AD) is critical as new pharmacotherapies are being developed. The ADAS-cog is considered the gold-standard and the most popular cognitive testing instrument used in clinical trials to detect changes in the core symptoms of AD.
This study critically looks at various factors that might influence the way the ADAS-cog is administered and therefore may lead to and yield unintended outcomes. The study found factors such as rater training, rater education, variance in time allotment during testing as well as rater experience and individual judgment may contribute to variance in scoring when using this assessment.
"Clinical trials for the possible treatment of Alzheimer's disease and other dementias are becoming more expansive and being run in many countries. The necessity for the primary outcome instrument to be administered consistently in different countries, cultures and between different clinical trials is critical if we are to determine which treatment works better than others. Any variability in how the instruments are administered can adversely affect the ability to detect positive outcomes," says Donald Connor PhD, PhD, director of neuropsychology at Banner Health's Sun Health Research Institute.
Rater experiences were not the only factors that contributed to variances in ADAS-cog scoring. The study also suggested that test materials changed over time including large ranges in the quality of naming materials, word card decks, instruction manuals and worksheets, all factors that can affect outcomes.
"Even as we try to develop better instruments for the detection of meaningful change we must make sure that our current instruments are utilized as effectively as possible," Dr. Connor says. "As the population continues to age rapidly and new Alzheimer's medications are being developed, it is critical that all who are involved in clinical evaluation and testing does so with precision and consistency."
The study is published in the November issue of the Journal of Alzheimer's Disease (Volume 15:3).
Moreover, this study further suggests that ADAS-Cog rater training and experience are factors that contribute to variances seen in this assessment tool.
The importance of a reliable diagnosis of the Alzheimer's disease (AD) is critical as new pharmacotherapies are being developed. The ADAS-cog is considered the gold-standard and the most popular cognitive testing instrument used in clinical trials to detect changes in the core symptoms of AD.
This study critically looks at various factors that might influence the way the ADAS-cog is administered and therefore may lead to and yield unintended outcomes. The study found factors such as rater training, rater education, variance in time allotment during testing as well as rater experience and individual judgment may contribute to variance in scoring when using this assessment.
"Clinical trials for the possible treatment of Alzheimer's disease and other dementias are becoming more expansive and being run in many countries. The necessity for the primary outcome instrument to be administered consistently in different countries, cultures and between different clinical trials is critical if we are to determine which treatment works better than others. Any variability in how the instruments are administered can adversely affect the ability to detect positive outcomes," says Donald Connor PhD, PhD, director of neuropsychology at Banner Health's Sun Health Research Institute.
Rater experiences were not the only factors that contributed to variances in ADAS-cog scoring. The study also suggested that test materials changed over time including large ranges in the quality of naming materials, word card decks, instruction manuals and worksheets, all factors that can affect outcomes.
"Even as we try to develop better instruments for the detection of meaningful change we must make sure that our current instruments are utilized as effectively as possible," Dr. Connor says. "As the population continues to age rapidly and new Alzheimer's medications are being developed, it is critical that all who are involved in clinical evaluation and testing does so with precision and consistency."
The study is published in the November issue of the Journal of Alzheimer's Disease (Volume 15:3).
Monday, November 17, 2008
UA Pharmacy Researcher To Study the Adverse Effects of Street Drug 'Ecstasy'
[Source : Karin Lorentzen, UA School of Pharmacy] - The National Institute on Drug Abuse has awarded a researcher at The University of Arizona College of Pharmacy $1.7 million for a nearly five-year study of the long-term adverse effects of the street drug ecstasy, also known as the “hug drug.
Terrence J. Monks, PhD, head of the college’s Department of Pharmacology and Toxicology and a BIO5 member, is a specialist in the study of drug toxicology, or the “bad” effects of drugs. He will be the principal investigator on the ecstasy project.
“Most research on ecstasy focuses on the pharmacological, or nontoxic effects of the drug,” says Monks. “My interest lies in learning how the drug negatively affects the brain.”
Classified as a Schedule I substance, ecstasy has been controlled in the United States since 1985. Ecstasy (also known as MDMA, or methylenedioxymethamphetamine) is a synthetic, psychoactive drug that is chemically similar to the stimulant methamphetamine. It produces an energizing effect as well as feelings of euphoria, emotional warmth, and distortions in time perception and tactile experiences.
These effects of MDMA have contributed to its popularity as a “party drug” among adolescents and young adults who frequent weekend-long “raves” or “techo-parties.” However, the drug has a serious down side.
“A number of adverse effects are associated with the use of MDMA,” says Monks. “MDMA use and abuse therefore has the potential to give rise to a major public health problem.”
According to the U.S. Department of State, the short-term negative effects of ecstasy can be nausea, dilated pupils, dry mouth and throat, and lower jaw tension. Use of the drug often leads to dramatic increases in body temperature exceeding 100 degrees Fahrenheit, which in turn can lead to muscle breakdown and kidney and cardiovascular system failure. This hyperthermic response can therefore result in fatal blood clotting, heart attacks and strokes.
Scientific studies have found that ecstasy use also produces long-term damage to the brain’s ability to release serotonin, which regulates mood, body temperature and memory.
“Ecstasy may be the only amphetamine-based drug that attacks the serotonin system,” says Monks. “There is little doubt that it has the potential to be toxic to the human nervous system. The question is how.”
Monks’ research will focus on the process by which ecstasy is metabolized by the body. When the drug enters the body orally in pill form (the manner in which it is usually taken), enzymes in the body convert it either to harmless metabolites or into toxic metabolites. Predicting which people process ecstasy into toxic metabolites more readily than other people is the challenge.
“Individuals metabolize ecstasy differently,” says Monks. “If 100 people take ecstasy, perhaps five will metabolize the drug very efficiently, whereas five others will metabolize the drug poorly. Since metabolism of ecstasy is required for it to produce neurotoxicity, the individual who efficiently metabolizes the drug will likely be more susceptible to the long-term adverse effects.”
The UA professor is believed to be the only researcher in the U.S. studying the role of metabolism in the neurotoxicity of the drug.
The results of Monks’ research will help people understand which individuals are more likely to suffer long-term negative effects of ecstasy.
“The multitude of adverse effects resulting from the misuse of ecstasy necessitates a complete understanding of the neuropharmacology and neurotoxicology of this unusual amphetamine derivative,” says Monks. “We hope to help define important factors that contribute to individual susceptibility to the long-term adverse effects of this drug.”
Terrence J. Monks, PhD, head of the college’s Department of Pharmacology and Toxicology and a BIO5 member, is a specialist in the study of drug toxicology, or the “bad” effects of drugs. He will be the principal investigator on the ecstasy project.
“Most research on ecstasy focuses on the pharmacological, or nontoxic effects of the drug,” says Monks. “My interest lies in learning how the drug negatively affects the brain.”
Classified as a Schedule I substance, ecstasy has been controlled in the United States since 1985. Ecstasy (also known as MDMA, or methylenedioxymethamphetamine) is a synthetic, psychoactive drug that is chemically similar to the stimulant methamphetamine. It produces an energizing effect as well as feelings of euphoria, emotional warmth, and distortions in time perception and tactile experiences.
These effects of MDMA have contributed to its popularity as a “party drug” among adolescents and young adults who frequent weekend-long “raves” or “techo-parties.” However, the drug has a serious down side.
“A number of adverse effects are associated with the use of MDMA,” says Monks. “MDMA use and abuse therefore has the potential to give rise to a major public health problem.”
According to the U.S. Department of State, the short-term negative effects of ecstasy can be nausea, dilated pupils, dry mouth and throat, and lower jaw tension. Use of the drug often leads to dramatic increases in body temperature exceeding 100 degrees Fahrenheit, which in turn can lead to muscle breakdown and kidney and cardiovascular system failure. This hyperthermic response can therefore result in fatal blood clotting, heart attacks and strokes.
Scientific studies have found that ecstasy use also produces long-term damage to the brain’s ability to release serotonin, which regulates mood, body temperature and memory.
“Ecstasy may be the only amphetamine-based drug that attacks the serotonin system,” says Monks. “There is little doubt that it has the potential to be toxic to the human nervous system. The question is how.”
Monks’ research will focus on the process by which ecstasy is metabolized by the body. When the drug enters the body orally in pill form (the manner in which it is usually taken), enzymes in the body convert it either to harmless metabolites or into toxic metabolites. Predicting which people process ecstasy into toxic metabolites more readily than other people is the challenge.
“Individuals metabolize ecstasy differently,” says Monks. “If 100 people take ecstasy, perhaps five will metabolize the drug very efficiently, whereas five others will metabolize the drug poorly. Since metabolism of ecstasy is required for it to produce neurotoxicity, the individual who efficiently metabolizes the drug will likely be more susceptible to the long-term adverse effects.”
The UA professor is believed to be the only researcher in the U.S. studying the role of metabolism in the neurotoxicity of the drug.
The results of Monks’ research will help people understand which individuals are more likely to suffer long-term negative effects of ecstasy.
“The multitude of adverse effects resulting from the misuse of ecstasy necessitates a complete understanding of the neuropharmacology and neurotoxicology of this unusual amphetamine derivative,” says Monks. “We hope to help define important factors that contribute to individual susceptibility to the long-term adverse effects of this drug.”
Friday, November 14, 2008
First Alana’s Champs 5K to fund TGen brain cancer efforts
[Source: TGen] - The first Alana's Champs 5K, a run and walk to benefit brain cancer research at the Translational Genomics Research Institute (TGen), is set for Dec. 6 at Wesley Bolin Memorial Plaza.
The event is named for Alana Lysholm-Bernacchi, a TGen neurogenomics researcher who studied hearing loss, Down syndrome and amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's Disease. She died as the result of a brain tumor on Dec. 3, 2007.
Alana's Champs 5K is coordinated by the TGen Foundation, Arizona Road Racers and by Brett Bernacchi, a TGen volunteer and the husband of Alana.
If you go
Where: Wesley Bolin Memorial Plaza, just east of the Arizona State Capitol, 1700 W. Washington St., Phoenix.
When: Dec. 6. Event-day registration starts at 7 a.m.; the 5-kilometer run starts at 8 a.m.; the 5K walk at 8:10 a.m.; and the 1-mile run/walk at 8:45 a.m., followed by a kids dash and raffle.
Participation Fees:-- Ages 13 and up: $20 if pre-registered by Nov. 16; $25 from Nov. 16-Dec. 5; and $30 on Dec. 6.-- Ages 5-12: $5 if pre-registered by Nov. 16; $10 from Nov. 15-Dec. 6.-- Children ages 4 and younger are free.
Details: Please visit the TGen Foundation at www.helptgen.org or call Erin Massey, assistant director of development, at 602-343-8470.
The event is named for Alana Lysholm-Bernacchi, a TGen neurogenomics researcher who studied hearing loss, Down syndrome and amyotrophic lateral sclerosis (ALS), often referred to as Lou Gehrig's Disease. She died as the result of a brain tumor on Dec. 3, 2007.
Alana's Champs 5K is coordinated by the TGen Foundation, Arizona Road Racers and by Brett Bernacchi, a TGen volunteer and the husband of Alana.
If you go
Where: Wesley Bolin Memorial Plaza, just east of the Arizona State Capitol, 1700 W. Washington St., Phoenix.
When: Dec. 6. Event-day registration starts at 7 a.m.; the 5-kilometer run starts at 8 a.m.; the 5K walk at 8:10 a.m.; and the 1-mile run/walk at 8:45 a.m., followed by a kids dash and raffle.
Participation Fees:-- Ages 13 and up: $20 if pre-registered by Nov. 16; $25 from Nov. 16-Dec. 5; and $30 on Dec. 6.-- Ages 5-12: $5 if pre-registered by Nov. 16; $10 from Nov. 15-Dec. 6.-- Children ages 4 and younger are free.
Details: Please visit the TGen Foundation at www.helptgen.org or call Erin Massey, assistant director of development, at 602-343-8470.
Monday, November 10, 2008
MRI reveals relationship between depression and pain
[Source: EurekAlert] - The brains of individuals with major depressive disorder appear to react more strongly when anticipating pain and also display altered functioning of the neural network that modifies pain sensitivity, according to a report in the November issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
"Chronic pain and depression are common and often overlapping syndromes," the authors write as background information in the article. Recurring or chronic pain occurs in more than 75 percent of patients with depression, and between 30 percent and 60 percent of patients with chronic pain report symptoms of depression "Understanding the neurobiological basis of this relationship is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder."
Irina A. Strigo, Ph.D., of the University of California San Diego, La Jolla, and colleagues studied 15 young adults with major depressive disorder (average age 24.5) who were not taking medication and 15 individuals who were the same age (average 24.3 years) and had the same education level but did not have depression. Patients with depression completed a questionnaire that evaluated their tendencies to magnify, ruminate over or feel helpless in the face of pain. All participants underwent functional magnetic resonance imaging (fMRI) while their arms were exposed to a thermal device heated to painful levels (an average of 46.4 degrees to 46.9 degrees Celsius, or about 115 degrees to 116 degrees Fahrenheit) and also to non-painful temperatures. Visual cues (a green shape for non-painful warmth and a red shape for painful warmth) were presented before the heat was applied.
Compared with the controls, patients with depression showed increased activation in certain areas of their brain—including the right amygdala—during the anticipation of painful stimuli. They also displayed increased activation in the right amygdala and decreased activation in other areas, including those responsible for pain modulation (adjusting sensitivity to pain), during the painful experience.
To examine whether the activation of the amygdala was associated with passive coping styles, the researchers compared the percentage change in the activations of the amygdala with the helplessness, rumination and ramification reported by the participants with depression.
"Significant positive correlations were observed in the major depressive disorder group between greater helplessness scores and greater activity in the right amygdala during the anticipation of pain," the authors write.
"The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptative modulation during the experience of heat pain," the authors write. "This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic."
"Future studies that directly examine whether maladaptive response to pain in major depressive disorder is due to emotional allodynia [a pain response to a non-painful stimulus], maladaptive control responses, lack of resilience and/or ineffectual recruitment of positive energy resources will further our understanding of pain-depression comorbidity," they conclude.
###
(Arch Gen Psychiatry. 2008;65[11]:1275-1284. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: This study was supported by Barrow Neurological Foundation, grants from the National Institute of Mental Health, the National Association for Research in Schizophrenia and Depression and the University of California San Diego Center of Excellence for Stress and Mental Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
"Chronic pain and depression are common and often overlapping syndromes," the authors write as background information in the article. Recurring or chronic pain occurs in more than 75 percent of patients with depression, and between 30 percent and 60 percent of patients with chronic pain report symptoms of depression "Understanding the neurobiological basis of this relationship is important because the presence of comorbid pain contributes significantly to poorer outcomes and increased cost of treatment in major depressive disorder."
Irina A. Strigo, Ph.D., of the University of California San Diego, La Jolla, and colleagues studied 15 young adults with major depressive disorder (average age 24.5) who were not taking medication and 15 individuals who were the same age (average 24.3 years) and had the same education level but did not have depression. Patients with depression completed a questionnaire that evaluated their tendencies to magnify, ruminate over or feel helpless in the face of pain. All participants underwent functional magnetic resonance imaging (fMRI) while their arms were exposed to a thermal device heated to painful levels (an average of 46.4 degrees to 46.9 degrees Celsius, or about 115 degrees to 116 degrees Fahrenheit) and also to non-painful temperatures. Visual cues (a green shape for non-painful warmth and a red shape for painful warmth) were presented before the heat was applied.
Compared with the controls, patients with depression showed increased activation in certain areas of their brain—including the right amygdala—during the anticipation of painful stimuli. They also displayed increased activation in the right amygdala and decreased activation in other areas, including those responsible for pain modulation (adjusting sensitivity to pain), during the painful experience.
To examine whether the activation of the amygdala was associated with passive coping styles, the researchers compared the percentage change in the activations of the amygdala with the helplessness, rumination and ramification reported by the participants with depression.
"Significant positive correlations were observed in the major depressive disorder group between greater helplessness scores and greater activity in the right amygdala during the anticipation of pain," the authors write.
"The anticipatory brain response may indicate hypervigilance to impending threat, which may lead to increased helplessness and maladaptative modulation during the experience of heat pain," the authors write. "This mechanism could in part explain the high comorbidity of pain and depression when these conditions become chronic."
"Future studies that directly examine whether maladaptive response to pain in major depressive disorder is due to emotional allodynia [a pain response to a non-painful stimulus], maladaptive control responses, lack of resilience and/or ineffectual recruitment of positive energy resources will further our understanding of pain-depression comorbidity," they conclude.
###
(Arch Gen Psychiatry. 2008;65[11]:1275-1284. Available pre-embargo to the media at www.jamamedia.org.)
Editor's Note: This study was supported by Barrow Neurological Foundation, grants from the National Institute of Mental Health, the National Association for Research in Schizophrenia and Depression and the University of California San Diego Center of Excellence for Stress and Mental Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Phoenix to get Parkinson's center, named after Ali
[Source: KTAR.Com] - St. Joseph's Hospital and Medical Center has announced plans for one of the most comprehensive Parkinson's centers in the country, named after former boxing champion Muhammad Ali and his wife, Lonnie.
The Alis were on hand Tuesday for the announcement about the Muhammad Ali Parkinson Center.
"To see the beginning of this beautiful new center is truly a dream come true for Muhammad and me," said Lonnie Ali. "We are so grateful to all of you -- to Dr. Abe Lieberman, the Celebrity Fight Night Foundation and other supporters.
The new center is expected to open in late 2009. It will include 10 basic exam rooms, a tremor exam room, a botox treatment room, a tilt room to help evaluate patients with orthostatic hypertension and a balance lab.
The pavilion also will contain treatment areas for physical therapy, occupational therapy and speech therapy and a multi-purpose room for educaton and recreational classes.
The National Institutes of Health says at least 500,000 people in the United States suffer from Parkinson's disease and approximately 50,000 new cases are reported annually. The incidence is expected to increase as baby boomers age.
St. Joseph's Hospital and its Barrow Neurological Institute are working to improve services for people with Parkinson's, Huntington's disease and Tourette syndrome.
"We're on our way to ecoming a world-class center for the growing number of people that are affected by these chronic illnesses," said Lieberman.
He added, "The Alis know that Muhammad Ali is going to get excellent care because he's Muhammad Ali, but they want everyone to get that same type of care."
The Alis were on hand Tuesday for the announcement about the Muhammad Ali Parkinson Center.
"To see the beginning of this beautiful new center is truly a dream come true for Muhammad and me," said Lonnie Ali. "We are so grateful to all of you -- to Dr. Abe Lieberman, the Celebrity Fight Night Foundation and other supporters.
The new center is expected to open in late 2009. It will include 10 basic exam rooms, a tremor exam room, a botox treatment room, a tilt room to help evaluate patients with orthostatic hypertension and a balance lab.
The pavilion also will contain treatment areas for physical therapy, occupational therapy and speech therapy and a multi-purpose room for educaton and recreational classes.
The National Institutes of Health says at least 500,000 people in the United States suffer from Parkinson's disease and approximately 50,000 new cases are reported annually. The incidence is expected to increase as baby boomers age.
St. Joseph's Hospital and its Barrow Neurological Institute are working to improve services for people with Parkinson's, Huntington's disease and Tourette syndrome.
"We're on our way to ecoming a world-class center for the growing number of people that are affected by these chronic illnesses," said Lieberman.
He added, "The Alis know that Muhammad Ali is going to get excellent care because he's Muhammad Ali, but they want everyone to get that same type of care."
Monday, November 3, 2008
Chronic Headaches? 'Medication Overuse Headaches' Surprisingly Common
[Source: ScienceDaily] - There is a critical need to review current treatment strategies for the increasingly common problem of medication overuse headaches (MOH), according to a series of international papers in the November issue of Cephalalgia.
“MOH is associated with severe disability, unmet treatment need and little clinical data to support current management strategies” says neurology expert Professor David W Dodick from the Mayo Clinic College of Medicine, Arizona, USA.
His overview also highlights the need for greater research into the condition - in particular the role that migraine medication can play in the withdrawal process. It is accompanied by papers on how the condition is tackled in Denmark, Germany, Moldova, Japan, Spain, Canada, India and Taiwan.
MOH, previously known as rebound headache, drug-induced headache or drug-misuse headache, is a headache that occurs at least 15 days a month when patients overuse medication.
“Tolerance to the analgesic effect of the acute medication develops over time, consumption may increase and patients may show withdrawal symptoms when they stop the overused mediation” explains Professor Dodick. “We estimate that the condition affects one in every 100 adults and one in every 200 adolescents worldwide, which is a considerable number.
“For example, in the USA 60 per cent of people with chronic daily headaches attending
headache clinics have MOH. Data from a physician study suggests that it may be the third most frequent type of headache after migraines and tension-type headaches. And a Norwegian study found that people were seven times more likely to suffer from chronic headaches if they used analgesics daily or almost daily for more than a month.”
Despite being very common, there are no standardised treatment guidelines for MOH, partly due to the small number of controlled clinical trials that have addressed the treatment of this condition.
However, recent research suggests that the traditional approach of not providing new treatment strategies until patients have been through detoxification may not be the best clinical option.
“Data from recent trials indicate that treatments developed to prevent migraine may prove effective if they are used in patients with MOH before the overused medicine is withdrawn” says Professor Dodick.
“This points to the need for clinical trials to re-evaluate current strategies and find the best way forward.”
The international papers that accompany Dr Dodick’s overview show that MOH is a common problem, but the incidence, causes and treatment vary from country to country.
•Just under a quarter of the MOH cases seen at Taipei Veterans General Hospital in Taiwan are caused by people overusing cold cure preparations. Dr Shuu-Jiun Wang points out that 100 brands are currently available in Taiwan and he and his colleagues frequently see patients who have taken the whole 60ml bottle rather than the 10ml recommended dose. The problem is more common in people with lower education levels. Other common causes of MOH, which affect one in 100 Taiwanese people, include analgesics, with or without caffeine.
•Dr Zaza Katsarava from the University of Essen in Germany reports that new rules that enable healthcare plans to sign contracts with headache centres to provide day care centre withdrawal programmes have reduced MOH relapse rates in the country. He says that studies lasting from three to five years have indicated that relapse rates range from 34 to 48 per cent.
•Medication overuse is a major clinical problem and a significant source of headache-related disability in Canada, according to Professor Werner J Becker from the University of Calgary. He believes that it will take a concerted effort by the public, health professionals and healthcare funders to provide better prevention and treatment for MOH. But he points out: “It can at times be difficult for patients to find a physician who will expend the time, energy and skill to help them escape from the prison of medication overuse.”
•MOH is a serious problem in Spain, especially among middle-aged women, says Professor Julio Pascual from the University Hospital at Salamanca. He advocates an active detection and treatment approach, pointing out that in his experience this can lead to long-term improvements in more than half of MOH cases. However he adds that patients with primary headache can often be biologically, and possibly genetically, predisposed to developing chronic daily headaches regardless of analgesic use, making the drugs the consequence, not the cause of daily headaches.
•Dr Rigmor Jensen from the University of Copenhagen, Denmark, says that MOH has become a greater problem in Scandinavia over the last decade and is now the third most prevalent form of headache after tension type headaches and migraine. “A long-standing tradition of restrictive use of painkillers is changing and in general the use of simple analgesics and combination drugs has steadily increased in Denmark” she says.
The drugs that cause MOH may vary from country to country says Dr Rie Kanki from Kitasato University in Kanagawa, Japan, as their market availability may differ and people’s attitudes can be greatly affected by cultural attitudes. For example codeine and barbiturates, which are used in combination analgesics in the USA and Europe, are not available in Japan. Dr Kanki says that patient education is essential and that the growing number of headache specialists in Japan is making it easier to seek expert advice.
People living in Moldova often face psychological, cultural and religious barriers to drug use, according to Dr Ion Moldovanu from the State Medical and Pharmaceutical University in Chisinau. He reports that a clinical study of chronic migraine patients found that the two-thirds who did not have MOH expressed significantly greater phobias about the effects of drugs. Because of this they used fewer drugs than the third of patients who did have MOH.
Limited clinical data suggests that MOH is not as prevalent in India as it is in Europe and the US, reports Dr K Ravishankar from the Lilavati Hospital and Research Centre in Mumbai. He suggests this could be because people tend to use pain balms, delay medication and use alternative medicine. However, he says that more population-based studies are needed in the country, where access to healthcare is difficult and costly and headaches are not a priority compared with AIDS, Malaria and TB.
“It is clear from the papers in this issue of Cephalalgia that MOH is a common universal problem and that many countries face unique challenges due to the drugs that are available, patient and physician attitudes and the different health care delivery systems” says Dr Dodick, who will take over as Editor-in-Chief of Cephalalgia in January 2009.
“However, the overwhelming consensus is that MOH is a growing problem that has a major negative impact on health-related quality of life. It is important to identify patients with a high frequency of headaches, who are at high risk of MOH, as early as possible and initiate measures to reduce the consumption of acute pain medication.
“This is an important series of papers as it illustrates the global public health burden imposed by MOH and identifies the unique underlying factors that contribute to MOH in different countries, as well as country-specific barriers to treatment.
“The expert authors have also highlighted the need for systematic and concerted research efforts to better understand the mechanisms and most effective treatment strategies for MOH, stressing that this is a major priority in the field of headache medicine.”
“MOH is associated with severe disability, unmet treatment need and little clinical data to support current management strategies” says neurology expert Professor David W Dodick from the Mayo Clinic College of Medicine, Arizona, USA.
His overview also highlights the need for greater research into the condition - in particular the role that migraine medication can play in the withdrawal process. It is accompanied by papers on how the condition is tackled in Denmark, Germany, Moldova, Japan, Spain, Canada, India and Taiwan.
MOH, previously known as rebound headache, drug-induced headache or drug-misuse headache, is a headache that occurs at least 15 days a month when patients overuse medication.
“Tolerance to the analgesic effect of the acute medication develops over time, consumption may increase and patients may show withdrawal symptoms when they stop the overused mediation” explains Professor Dodick. “We estimate that the condition affects one in every 100 adults and one in every 200 adolescents worldwide, which is a considerable number.
“For example, in the USA 60 per cent of people with chronic daily headaches attending
headache clinics have MOH. Data from a physician study suggests that it may be the third most frequent type of headache after migraines and tension-type headaches. And a Norwegian study found that people were seven times more likely to suffer from chronic headaches if they used analgesics daily or almost daily for more than a month.”
Despite being very common, there are no standardised treatment guidelines for MOH, partly due to the small number of controlled clinical trials that have addressed the treatment of this condition.
However, recent research suggests that the traditional approach of not providing new treatment strategies until patients have been through detoxification may not be the best clinical option.
“Data from recent trials indicate that treatments developed to prevent migraine may prove effective if they are used in patients with MOH before the overused medicine is withdrawn” says Professor Dodick.
“This points to the need for clinical trials to re-evaluate current strategies and find the best way forward.”
The international papers that accompany Dr Dodick’s overview show that MOH is a common problem, but the incidence, causes and treatment vary from country to country.
•Just under a quarter of the MOH cases seen at Taipei Veterans General Hospital in Taiwan are caused by people overusing cold cure preparations. Dr Shuu-Jiun Wang points out that 100 brands are currently available in Taiwan and he and his colleagues frequently see patients who have taken the whole 60ml bottle rather than the 10ml recommended dose. The problem is more common in people with lower education levels. Other common causes of MOH, which affect one in 100 Taiwanese people, include analgesics, with or without caffeine.
•Dr Zaza Katsarava from the University of Essen in Germany reports that new rules that enable healthcare plans to sign contracts with headache centres to provide day care centre withdrawal programmes have reduced MOH relapse rates in the country. He says that studies lasting from three to five years have indicated that relapse rates range from 34 to 48 per cent.
•Medication overuse is a major clinical problem and a significant source of headache-related disability in Canada, according to Professor Werner J Becker from the University of Calgary. He believes that it will take a concerted effort by the public, health professionals and healthcare funders to provide better prevention and treatment for MOH. But he points out: “It can at times be difficult for patients to find a physician who will expend the time, energy and skill to help them escape from the prison of medication overuse.”
•MOH is a serious problem in Spain, especially among middle-aged women, says Professor Julio Pascual from the University Hospital at Salamanca. He advocates an active detection and treatment approach, pointing out that in his experience this can lead to long-term improvements in more than half of MOH cases. However he adds that patients with primary headache can often be biologically, and possibly genetically, predisposed to developing chronic daily headaches regardless of analgesic use, making the drugs the consequence, not the cause of daily headaches.
•Dr Rigmor Jensen from the University of Copenhagen, Denmark, says that MOH has become a greater problem in Scandinavia over the last decade and is now the third most prevalent form of headache after tension type headaches and migraine. “A long-standing tradition of restrictive use of painkillers is changing and in general the use of simple analgesics and combination drugs has steadily increased in Denmark” she says.
The drugs that cause MOH may vary from country to country says Dr Rie Kanki from Kitasato University in Kanagawa, Japan, as their market availability may differ and people’s attitudes can be greatly affected by cultural attitudes. For example codeine and barbiturates, which are used in combination analgesics in the USA and Europe, are not available in Japan. Dr Kanki says that patient education is essential and that the growing number of headache specialists in Japan is making it easier to seek expert advice.
People living in Moldova often face psychological, cultural and religious barriers to drug use, according to Dr Ion Moldovanu from the State Medical and Pharmaceutical University in Chisinau. He reports that a clinical study of chronic migraine patients found that the two-thirds who did not have MOH expressed significantly greater phobias about the effects of drugs. Because of this they used fewer drugs than the third of patients who did have MOH.
Limited clinical data suggests that MOH is not as prevalent in India as it is in Europe and the US, reports Dr K Ravishankar from the Lilavati Hospital and Research Centre in Mumbai. He suggests this could be because people tend to use pain balms, delay medication and use alternative medicine. However, he says that more population-based studies are needed in the country, where access to healthcare is difficult and costly and headaches are not a priority compared with AIDS, Malaria and TB.
“It is clear from the papers in this issue of Cephalalgia that MOH is a common universal problem and that many countries face unique challenges due to the drugs that are available, patient and physician attitudes and the different health care delivery systems” says Dr Dodick, who will take over as Editor-in-Chief of Cephalalgia in January 2009.
“However, the overwhelming consensus is that MOH is a growing problem that has a major negative impact on health-related quality of life. It is important to identify patients with a high frequency of headaches, who are at high risk of MOH, as early as possible and initiate measures to reduce the consumption of acute pain medication.
“This is an important series of papers as it illustrates the global public health burden imposed by MOH and identifies the unique underlying factors that contribute to MOH in different countries, as well as country-specific barriers to treatment.
“The expert authors have also highlighted the need for systematic and concerted research efforts to better understand the mechanisms and most effective treatment strategies for MOH, stressing that this is a major priority in the field of headache medicine.”
UCB boosted by US approval for epilepsy drug Vimpat
[Source: Kevin Grogan, PharmaTimes] - UCB’s stock has soared on the news that the Belgian firm’s epilepsy drug Vimpat has been given the green light by US regulators.
The US Food and Drug Administration has approved Vimpat (lacosamide) for use as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are 17 and older. The approval is based on one Phase II and two Phase III trials of 1,300 people and before adding Vimpat, patients experienced a median baseline seizure frequency ranging from 10 to 17 seizures per month, despite being on one to three other antiepileptics; 45.2% of patients had previously tried seven or more AEDs to control their seizures.
In the studies, patients randomised to Vimpat had their seizures reduced by half and experienced reductions in median seizure frequency at rates that were significantly greater than those in placebo groups. In preclinical studies, Vimpat has been shown to bind to the collapsin response mediator protein-2, an important target that affects the way that nerves differentiate and grow. However, the precise nature of the interaction between the drug and CRMP-2 and between the latter and seizure control is not known.
Lead investigator Steven Chung at the Barrow Neurological Institute in Phoenix said that “Vimpat is unique because it works unlike any other antiepileptic drug that is currently available”. He added that it should be considered for patients who have uncontrolled seizures with their current treatment regimen, “no matter how many previous AEDS they've tried”.
Vimpat, which is approved in Europe and was recently launched in the UK and Germany, is seen as a vital element in plugging the gap in sales facing UCB from the loss of patent protection on the allergy drug Zyrtec (cetirizine) last year and the antiepileptic Keppra (levetiracetam) in the near future.
However hopes are high that Vimpat could follow Keppra and become a blockbuster. The scientific community is also impressed with the compound according to its reaction to data presented at the European Congress on Epileptology in Berlin last month.
At the meeting in Germany, Elinor Ben-Menachem at the Institute for Clinical Neurosciences at the Sahlgrenska Academy in Gothenburg, Sweden, said that the pharmacokinetic profile of Vimpat is excellent. Lacosamide was completely absorbed in trials and can also be used with a wide range of other drugs patients may be taking for other conditions, such as metformin for diabetes, digoxin for herart failure and oral contraceptives.
Prof Menachem told PharmaTimes World News that the side effect profile of Vimpat is excellent and another advantage is that Vimpat will be available in three formulations – tablets, syrup and an intravenous injection. This is important especially in a hospital setting where patients in seizure need alternatives for administration.
The US Food and Drug Administration has approved Vimpat (lacosamide) for use as an add-on therapy for the treatment of partial-onset seizures in people with epilepsy who are 17 and older. The approval is based on one Phase II and two Phase III trials of 1,300 people and before adding Vimpat, patients experienced a median baseline seizure frequency ranging from 10 to 17 seizures per month, despite being on one to three other antiepileptics; 45.2% of patients had previously tried seven or more AEDs to control their seizures.
In the studies, patients randomised to Vimpat had their seizures reduced by half and experienced reductions in median seizure frequency at rates that were significantly greater than those in placebo groups. In preclinical studies, Vimpat has been shown to bind to the collapsin response mediator protein-2, an important target that affects the way that nerves differentiate and grow. However, the precise nature of the interaction between the drug and CRMP-2 and between the latter and seizure control is not known.
Lead investigator Steven Chung at the Barrow Neurological Institute in Phoenix said that “Vimpat is unique because it works unlike any other antiepileptic drug that is currently available”. He added that it should be considered for patients who have uncontrolled seizures with their current treatment regimen, “no matter how many previous AEDS they've tried”.
Vimpat, which is approved in Europe and was recently launched in the UK and Germany, is seen as a vital element in plugging the gap in sales facing UCB from the loss of patent protection on the allergy drug Zyrtec (cetirizine) last year and the antiepileptic Keppra (levetiracetam) in the near future.
However hopes are high that Vimpat could follow Keppra and become a blockbuster. The scientific community is also impressed with the compound according to its reaction to data presented at the European Congress on Epileptology in Berlin last month.
At the meeting in Germany, Elinor Ben-Menachem at the Institute for Clinical Neurosciences at the Sahlgrenska Academy in Gothenburg, Sweden, said that the pharmacokinetic profile of Vimpat is excellent. Lacosamide was completely absorbed in trials and can also be used with a wide range of other drugs patients may be taking for other conditions, such as metformin for diabetes, digoxin for herart failure and oral contraceptives.
Prof Menachem told PharmaTimes World News that the side effect profile of Vimpat is excellent and another advantage is that Vimpat will be available in three formulations – tablets, syrup and an intravenous injection. This is important especially in a hospital setting where patients in seizure need alternatives for administration.
Wednesday, October 29, 2008
Ultrasound Shown To Exert Remote Control Of Brain Circuits
[Source: ScienceDaily] - In a twist on nontraditional uses of ultrasound, a group of neuroscientists at Arizona State University has developed pulsed ultrasound techniques that can remotely stimulate brain circuit activity.
Their findings, published in the Oct. 29 issue of the journal Public Library of Science (PLoS) One, provide insights into how low-power ultrasound can be harnessed for the noninvasive neurostimulation of brain circuits and offers the potential for new treatments of brain disorders and disease.
While it might be hard to imagine the day where doctors could treat post traumatic stress disorders, traumatic brain injury and even Alzheimer's disease with the flip of a switch, most of us have in fact experienced some of ultrasound's numerous applications in our daily lives. For example, ultrasound has been used in fetal and other diagnostic medical imaging, ultrasonic teeth cleaning, physiotherapies, or surgical ablation. Ultrasound also provides a multitude of other non-medical uses, including pharmaceutical manufacturing, food processing, nondestructive materials testing, sonar, communications, oceanography and acoustic mapping.
"Studies of ultrasound and its interactions with biological tissues have a rich history dating back to the late 1920s," lead investigator William "Jamie" Tyler points out. "Several research groups have, for more than a half-century, demonstrated that ultrasound can produce changes in excitable tissues, such as nerve and/or muscle, but detailed studies in neurons at the cellular level have been lacking."
"We were able to unravel how ultrasound can stimulate the electrical activity of neurons by optically monitoring the activity of neuronal circuits, while we simultaneously propagated low-intensity, low-frequency ultrasound through brain tissues," says Tyler, assistant professor of neurobiology and bioimaging in the School of Life Sciences in the College of Liberal Arts and Sciences.
Led by Tyler, the ASU research group discovered that remotely delivered low intensity, low frequency ultrasound (LILFU) increased the activity of voltage-gated sodium and calcium channels in a manner sufficient to trigger action potentials and the release of neurotransmitter from synapses. Since these processes are fundamental to the transfer of information among neurons, the authors pose that this type of ultrasound provides a powerful new tool for modulating the activity of neural circuits.
"Many of the stimulation methods used by neuroscientists require the use and implantation of stimulating electrodes, requiring direct contact with nervous tissue or the introduction of exogenous proteins, such as those used for the light-activation of neurons," Tyler explains.
The search for new types of noninvasive neurostimulation methods led them to revisit ultrasound.
"We were quite surprised to find that ultrasound at power levels lower than those typically used in routine diagnostic medical imaging procedures could produce an increase in the activity of neurons while higher power levels produced very little effect on their activity," Tyler says.
Other neuroscientists and engineers have also been rapidly developing new neurostimulation methods for controlling nervous system activity and several approaches show promise for the treatment of a wide variety of nervous system disorders. For example, Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) have been shown to be effective in the management of psychiatric disorders such as depression, bipolar disorders, post-traumatic stress disorder, and drug addition, as well as for therapies of neurological diseases such as Parkinson's disease, Alzheimer's disease, Tourette Syndrome, epilepsy, dystonia, stuttering, tinnitus, recovery of cognitive and motor function following stroke, and chronic pain. Up until now, these two techniques have captured the attention of physicians and scientists; however, these therapies still pose risks to patients because they require the surgical implantation of stimulating electrodes. Thus, these types of therapies are often only available to patients presenting the worst of prognoses.
One prior stumbling block to using ultrasound noninvasively in the brain has been the skull. However, the acoustic frequencies utilized by Tyler and his colleagues to construct their pulsed ultrasound waveforms, overlap with a frequency range where optimal energy gains are achieved between transcranial transmission and brain absorption of ultrasound – which allows the ultrasound to penetrate bone and yet prevent damage to the soft tissues. Their findings are supported by other studies examining the potential of high-intensity focused ultrasound for ablating brain tissues, where it was shown that low-frequency ultrasound could be focused through human skulls.
When asked about the potential of using his groups' methods to remotely control brain activity, Tyler says: "One might be able to envision potential applications ranging from medical interventions to use in video gaming or the creation of artificial memories along the lines of Arnold Schwarzenegger's character in 'Total Recall.' Imagine taking a vacation without actually going anywhere?
"Obviously, we need to conduct further research and development, but one of the most exhilarating prospects is that low intensity, low frequency ultrasound permit deep-brain stimulation procedures without requiring exogenous proteins or surgically implanted medical devices," he adds.
Tyler and the other ASU researchers will now focus on further characterization of the influence of ultrasound on intact brain circuits and translational research, taking low intensity ultrasound from the lab into pre-clinical trials and treatment of neurological diseases.
Their findings, published in the Oct. 29 issue of the journal Public Library of Science (PLoS) One, provide insights into how low-power ultrasound can be harnessed for the noninvasive neurostimulation of brain circuits and offers the potential for new treatments of brain disorders and disease.
While it might be hard to imagine the day where doctors could treat post traumatic stress disorders, traumatic brain injury and even Alzheimer's disease with the flip of a switch, most of us have in fact experienced some of ultrasound's numerous applications in our daily lives. For example, ultrasound has been used in fetal and other diagnostic medical imaging, ultrasonic teeth cleaning, physiotherapies, or surgical ablation. Ultrasound also provides a multitude of other non-medical uses, including pharmaceutical manufacturing, food processing, nondestructive materials testing, sonar, communications, oceanography and acoustic mapping.
"Studies of ultrasound and its interactions with biological tissues have a rich history dating back to the late 1920s," lead investigator William "Jamie" Tyler points out. "Several research groups have, for more than a half-century, demonstrated that ultrasound can produce changes in excitable tissues, such as nerve and/or muscle, but detailed studies in neurons at the cellular level have been lacking."
"We were able to unravel how ultrasound can stimulate the electrical activity of neurons by optically monitoring the activity of neuronal circuits, while we simultaneously propagated low-intensity, low-frequency ultrasound through brain tissues," says Tyler, assistant professor of neurobiology and bioimaging in the School of Life Sciences in the College of Liberal Arts and Sciences.
Led by Tyler, the ASU research group discovered that remotely delivered low intensity, low frequency ultrasound (LILFU) increased the activity of voltage-gated sodium and calcium channels in a manner sufficient to trigger action potentials and the release of neurotransmitter from synapses. Since these processes are fundamental to the transfer of information among neurons, the authors pose that this type of ultrasound provides a powerful new tool for modulating the activity of neural circuits.
"Many of the stimulation methods used by neuroscientists require the use and implantation of stimulating electrodes, requiring direct contact with nervous tissue or the introduction of exogenous proteins, such as those used for the light-activation of neurons," Tyler explains.
The search for new types of noninvasive neurostimulation methods led them to revisit ultrasound.
"We were quite surprised to find that ultrasound at power levels lower than those typically used in routine diagnostic medical imaging procedures could produce an increase in the activity of neurons while higher power levels produced very little effect on their activity," Tyler says.
Other neuroscientists and engineers have also been rapidly developing new neurostimulation methods for controlling nervous system activity and several approaches show promise for the treatment of a wide variety of nervous system disorders. For example, Deep Brain Stimulation (DBS) and Vagal Nerve Stimulation (VNS) have been shown to be effective in the management of psychiatric disorders such as depression, bipolar disorders, post-traumatic stress disorder, and drug addition, as well as for therapies of neurological diseases such as Parkinson's disease, Alzheimer's disease, Tourette Syndrome, epilepsy, dystonia, stuttering, tinnitus, recovery of cognitive and motor function following stroke, and chronic pain. Up until now, these two techniques have captured the attention of physicians and scientists; however, these therapies still pose risks to patients because they require the surgical implantation of stimulating electrodes. Thus, these types of therapies are often only available to patients presenting the worst of prognoses.
One prior stumbling block to using ultrasound noninvasively in the brain has been the skull. However, the acoustic frequencies utilized by Tyler and his colleagues to construct their pulsed ultrasound waveforms, overlap with a frequency range where optimal energy gains are achieved between transcranial transmission and brain absorption of ultrasound – which allows the ultrasound to penetrate bone and yet prevent damage to the soft tissues. Their findings are supported by other studies examining the potential of high-intensity focused ultrasound for ablating brain tissues, where it was shown that low-frequency ultrasound could be focused through human skulls.
When asked about the potential of using his groups' methods to remotely control brain activity, Tyler says: "One might be able to envision potential applications ranging from medical interventions to use in video gaming or the creation of artificial memories along the lines of Arnold Schwarzenegger's character in 'Total Recall.' Imagine taking a vacation without actually going anywhere?
"Obviously, we need to conduct further research and development, but one of the most exhilarating prospects is that low intensity, low frequency ultrasound permit deep-brain stimulation procedures without requiring exogenous proteins or surgically implanted medical devices," he adds.
Tyler and the other ASU researchers will now focus on further characterization of the influence of ultrasound on intact brain circuits and translational research, taking low intensity ultrasound from the lab into pre-clinical trials and treatment of neurological diseases.
Thursday, October 16, 2008
Banner Thunderbird Medical Center to add more-precise cancer treatment
[Source: Carrie Watters, The Arizona Republic] - Banner Thunderbird Medical Center this month will install a machine that makes radiation treatments more precise and less time-consuming.
The $3.1 million piece of technology also will save on trips to Phoenix.
The central Glendale hospital will be the first in the West Valley to offer patients
Banner is partnering with neurosurgeons from Barrow Neurological Institute of St. Joseph's Hospital in Phoenix. The doctors will travel to Glendale to more conveniently provide this specialized treatment to West Valley residents.
In addition to the precise brain-tumor treatments, the technology will improve radiation treatment for other cancer patients.
The "latest and greatest" technology is more precise, said Robin Johnson, director of the radiation oncology department.
"It makes sure the tumor is receiving treatment and not the area around it," she said.
It's also a lot faster, which counts when lying on a hard table undergoing radiation treatment. Time should be reduced from 10 to 30 minutes to two to 10 minutes.
Banner provides radiation treatment to about 350 new patients each year and expects its cases could see a 10 percent increase with the upgraded equipment, which should be fully operational by January.
The equipment is called the Elekta Axesse machine, and Banner Thunderbird will be the third medical facility in the country to offer it.
This is the start of increased cancer-care options in the works at Banner Thunderbird.
The hospital, Glendale's largest private employer, will open a 200-bed tower next spring. That opening should allow for reorganization of existing space and offer room for expansion.
"Our focus will go to growing cancer care," Johnson said.
The $3.1 million piece of technology also will save on trips to Phoenix.
The central Glendale hospital will be the first in the West Valley to offer patients
Banner is partnering with neurosurgeons from Barrow Neurological Institute of St. Joseph's Hospital in Phoenix. The doctors will travel to Glendale to more conveniently provide this specialized treatment to West Valley residents.
In addition to the precise brain-tumor treatments, the technology will improve radiation treatment for other cancer patients.
The "latest and greatest" technology is more precise, said Robin Johnson, director of the radiation oncology department.
"It makes sure the tumor is receiving treatment and not the area around it," she said.
It's also a lot faster, which counts when lying on a hard table undergoing radiation treatment. Time should be reduced from 10 to 30 minutes to two to 10 minutes.
Banner provides radiation treatment to about 350 new patients each year and expects its cases could see a 10 percent increase with the upgraded equipment, which should be fully operational by January.
The equipment is called the Elekta Axesse machine, and Banner Thunderbird will be the third medical facility in the country to offer it.
This is the start of increased cancer-care options in the works at Banner Thunderbird.
The hospital, Glendale's largest private employer, will open a 200-bed tower next spring. That opening should allow for reorganization of existing space and offer room for expansion.
"Our focus will go to growing cancer care," Johnson said.
Monday, September 29, 2008
The BeamPath NEURO System: First Flexible CO2 Laser Scalpel
[Source: www.MedGadget.com] - OmniGuide, Inc. (Cambridge, MA) has recently announced their new BeamPath NEURO™ flexible CO2 laser for neurosurgery. According to the company, it is the first flexible CO2 laser scalpel out there. The big idea is to allow neurosurgeons to perform precise dissection, cutting, debulking, and microvascular coagulation using a hand-held, no-touch instrument, that is portable and flexible.
Robert F. Spetzler, M.D., F.A.C.S., Director, Barrow Neurological Institute, J.N. Harbor Chairman of Neurological Surgery in Phoenix, is quoted in the press release: "Neurosurgeons have long realized the benefits of CO2 lasers for microsurgery, but the traditional means of delivering the laser were too rigid and unwieldy for microsurgery, limiting lasers' use in our specialty, A flexible CO2 laser is ideal for removing small tumors that are in close proximity to critical structures, including very sensitive areas of the brain and spinal cord, as well as for tumors in deep holes, when the most precise, no-touch surgical tool is essential. A flexible CO2 laser is ideal for removing small tumors that are in close proximity to critical structures, including very sensitive areas of the brain and spinal cord, as well as for tumors in deep holes, when the most precise, no-touch surgical tool is essential."
The BeamPath NEURO system is designed to be used for various central nervous system (CNS) procedures, including intracranial tumor reserctions, spine tumor surgeries and transnasal pituitary procedures.
More about the company's proprietary BeamPath™ technology:
OmniGuide’s BeamPath™ photonic bandgap fibers are the world’s first solid state structure-based transmitters. Within each fiber, over forty microscopic layers of alternating glass and polymer form a reflective system known as a Bragg diffraction grating. The wavelength of light transmitted by this structure is a function of the thickness of the glass/ polymer bi-layers, which can be easily varied. Thus the BeamPath™ fibers can be scaled to channel different wavelengths of light. This approach represents a new paradigm in the field of light transmission, and resolves all of the limitations inherent in conventional fiber optics.
OmniGuide has also mastered a manufacturing process through which semiconductor/ polymer multi-layers can be manufactured in a scalable manner, to tolerances that were previously seen only in the semiconductor industry. The manufacturing breakthrough that made this possible is a system of drawing out a foot-long “preform” with millimeter-thick layers, into hundreds of meters of fiber with micron-thick layers.
Shifty eye movements behind famous optical illusion
[Source: New Scientist, David Robson] - The cause of an optical illusion, made famous by a 1981 painting, has finally been solved.
Neuroscientists have shown that the way our eyes constantly make tiny movements is responsible for the way concentric circles in Isia Leviant's painting 'Enigma' (see image, right) seem to flow before onlookers' eyes.
Susana Martinez-Conde and her team from the Barrow Neurological Institute in Phoenix, Arizona, tested whether the effect was down to tiny, involuntary jerks of the eyes, known as microsaccades. Their purpose is not fully understood, but the rate of these movements is known to vary naturally.
In the team's experiment, while three subjects viewed Enigma, cameras recorded their eye movements 500 times every second. The subjects were asked to press a button when the speed of the optical "trickle" of the illusion appeared to slow down or stop, and release it when the trickle seemed faster.
Faster flicker
Accounting for the reaction time required to press the button, the results showed that the illusion became more pronounced when microsaccades were happening at a faster rate. When the rate slowed to a stop, the illusion vanished.
Those results go against earlier findings that suggested eye movements were not responsible for the effect.
A previous study involved giving volunteers contact lenses with tiny stalks attached that held a version of the illusion, ensuring, the team thought, that it was always stationary relative to the eye. The volunteers still experienced the illusion, suggesting that the brain actually caused the phenomenon.
But the effect of microsaccades was not taken into account, says Martinez-Conde, since the contact lenses do not keep pace with the eye during such rapid, jerky movements.
"We can now rule out the idea that the illusion originates solely in the brain," she told New Scientist.
Martinez-Conde adds that their research may also explain other similar illusions, such as Bridget Riley's Fall, or the Ouchi illusion. "It would be unexpected if Enigma is the only illusion affected by eye movements," she says.
However, the researchers are still in the dark as to what brain processes link the eye movements and the perception of an illusion. They intend to develop new experiments to find out.
Journal reference: PNAS (DOI: 10.1073/pnas.0709389105)
Tuesday, September 23, 2008
New dawn for Aimee after brain surgery
[Source: Daily Mercury] - AS the sun rises over Phoenix in Arizona, Aimee Anderson awakes to a new day she never thought she would see.
The young mum is on the slow road to recovery after a gruelling eight-hour operation to remove a brain stem cavernoma on Tuesday, September 9.
Thanks to the generosity of the Moranbah mining community she was able to go to America and undergo lifesaving surgery at a cost of $250,000.
Rachel Gobourn said her sister-in-law left hospital at the weekend.
"She's spending this week doing some physio work in the pool because her left arm is still a bit sluggish.
"She's having hospital check ups throughout the week, but otherwise, her recovery to date has been excellent."
Mr Anderson and his wife's neurosurgeon Robert Spetzler were pleased with the way the operation went.
"It looks like Dr Spetzler got all of the cavernoma," he said.
"Although, when he went in to operate it showed she had not one cavernoma, but four more growing in the same area. "The operation was also watched on the viewing platform by six European surgeons."
The $250,000 procedure at the renowned Barrow Neurological Institute was made possible by workers from Goonyella Riverside and Peak Downs mines.
Employees at each site donated safety bonuses, from 50 days free from Classified Injuries, towards Ms Anderson's life-saving surgery.
Around $50,000 from each site was collected.
Their money was matched dollar for dollar by the BHP Billiton Matched Giving Program.
The mining company also paid for her flights, accommodation, car hire and extra medical expenses.
The young mum is on the slow road to recovery after a gruelling eight-hour operation to remove a brain stem cavernoma on Tuesday, September 9.
Thanks to the generosity of the Moranbah mining community she was able to go to America and undergo lifesaving surgery at a cost of $250,000.
Rachel Gobourn said her sister-in-law left hospital at the weekend.
"She's spending this week doing some physio work in the pool because her left arm is still a bit sluggish.
"She's having hospital check ups throughout the week, but otherwise, her recovery to date has been excellent."
Mr Anderson and his wife's neurosurgeon Robert Spetzler were pleased with the way the operation went.
"It looks like Dr Spetzler got all of the cavernoma," he said.
"Although, when he went in to operate it showed she had not one cavernoma, but four more growing in the same area. "The operation was also watched on the viewing platform by six European surgeons."
The $250,000 procedure at the renowned Barrow Neurological Institute was made possible by workers from Goonyella Riverside and Peak Downs mines.
Employees at each site donated safety bonuses, from 50 days free from Classified Injuries, towards Ms Anderson's life-saving surgery.
Around $50,000 from each site was collected.
Their money was matched dollar for dollar by the BHP Billiton Matched Giving Program.
The mining company also paid for her flights, accommodation, car hire and extra medical expenses.
Monday, September 15, 2008
TGen investigators devise faster, cheaper way of analyzing the human genome
[Source: TGen] - Investigators at the Translational Genomics Research Institute (TGen) today announced a faster and less expensive way for scientists to find which genes might affect human health.
Using bar-codes, not unlike what shoppers find in grocery stores, TGen researchers found a way to index portions of the nearly 3-billion-base human genetic code, making it easier for scientists to zero in on the regions most likely to show variations in genetic traits.
The findings were published today in the online version of the journal Nature Methods. The study will be published in print in the journal's October edition.
Dr. David Craig, associate director of TGen's Neurogenomics Division, said the new method should cost only one-tenth, or less, of the current cost of sequencing genes commonly done to analyze Single Nucleotide Polymorphisms (SNPs), and in performing Genome-Wide Association (GWA) studies.
"Our goal is to find the genetic basis of disease," said Craig, the study's lead author. "It (the new method) provides us a way to immediately use next-generation sequencing technology for studying hundreds to thousands of individuals."
John Pearson, the head of TGen's Bioinformatics Research Unit, said the new method would allow scientists worldwide to more easily tune their sequencing experiments, and conduct their experiments with greater speed.
"In many cases, rather than sequencing the whole genome for 10 people, researchers would rather sequence a dozen genes for 1,000 people," said Pearson, who contributed to the study.
TGen scientists adapted an exciting new technology known as "next generation sequencing" to allow samples to be run and analyzed using 15 well-characterized indexes.
"Moving forward, TGen scientists are now attempting to merge this indexing approach with sequence-capture methods currently under development in their laboratories, which would likely further improve the cost savings and speed," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division, who also contributed to the study.
Depending on assumptions made in an experiment, the desired coverage -- and as a consequence, the cost -- can vary substantially, the study said, depending on whether the objective is:
Discovering genetic variants for genotyping by a separate method such as custom SNP genotyping.
Conducting polymorphism discovery and variant calling within one sequencing experiment.
Exhaustively resequencing for all common and rare variants.
The new method of analyzing human genetics should enable scientists at TGen and elsewhere to push ahead with key scientific research needed to prevent, diagnosis and treat a variety of diseases and conditions.
"Although whole-genome sequencing may be the primary motivator for improvements in sequencing technology," the study said, "it is clear that next-generation technologies are immediately useful for focused, hypothesis-driven sequencing of linkage peaks, groupings of candidate genes or sequencing the entire known coding sequence of the human genome."
Using bar-codes, not unlike what shoppers find in grocery stores, TGen researchers found a way to index portions of the nearly 3-billion-base human genetic code, making it easier for scientists to zero in on the regions most likely to show variations in genetic traits.
The findings were published today in the online version of the journal Nature Methods. The study will be published in print in the journal's October edition.
Dr. David Craig, associate director of TGen's Neurogenomics Division, said the new method should cost only one-tenth, or less, of the current cost of sequencing genes commonly done to analyze Single Nucleotide Polymorphisms (SNPs), and in performing Genome-Wide Association (GWA) studies.
"Our goal is to find the genetic basis of disease," said Craig, the study's lead author. "It (the new method) provides us a way to immediately use next-generation sequencing technology for studying hundreds to thousands of individuals."
John Pearson, the head of TGen's Bioinformatics Research Unit, said the new method would allow scientists worldwide to more easily tune their sequencing experiments, and conduct their experiments with greater speed.
"In many cases, rather than sequencing the whole genome for 10 people, researchers would rather sequence a dozen genes for 1,000 people," said Pearson, who contributed to the study.
TGen scientists adapted an exciting new technology known as "next generation sequencing" to allow samples to be run and analyzed using 15 well-characterized indexes.
"Moving forward, TGen scientists are now attempting to merge this indexing approach with sequence-capture methods currently under development in their laboratories, which would likely further improve the cost savings and speed," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division, who also contributed to the study.
Depending on assumptions made in an experiment, the desired coverage -- and as a consequence, the cost -- can vary substantially, the study said, depending on whether the objective is:
Discovering genetic variants for genotyping by a separate method such as custom SNP genotyping.
Conducting polymorphism discovery and variant calling within one sequencing experiment.
Exhaustively resequencing for all common and rare variants.
The new method of analyzing human genetics should enable scientists at TGen and elsewhere to push ahead with key scientific research needed to prevent, diagnosis and treat a variety of diseases and conditions.
"Although whole-genome sequencing may be the primary motivator for improvements in sequencing technology," the study said, "it is clear that next-generation technologies are immediately useful for focused, hypothesis-driven sequencing of linkage peaks, groupings of candidate genes or sequencing the entire known coding sequence of the human genome."
International TGen-led team finds link between brain protein and Alzheimer's disease
[Source: TGen] - Investigators at the Translational Genomics Research Institute (TGen) today announced a link between the brain protein KIBRA and Alzheimer's disease, a discovery that could lead to promising new treatments for this memory-robbing disorder.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
The new discovery builds on a previous TGen-led study published in the prestigious journal Science, which showed a genetic link between KIBRA and memory in healthy adults.
In the new study, TGen researchers found that carriers of a memory-enhancing flavor of the KIBRA gene had a 25 percent lower risk of developing Alzheimer's disease.
The findings were reported Saturday in the online edition of Neurobiology of Aging, a Philadelphia-based peer-review journal that generally focuses on how aging affects the nervous system.
"This research suggests that KIBRA, and possibly some of the proteins with which it interacts, may play a role in Alzheimer's disease," said Dr. Matthew Huentelman, an investigator in TGen's Neurogenomics Division and the paper's senior author.
The critical difference found in KIBRA, a protein so named because it is commonly found in the kidneys and brain, was that those individuals with the T-allele gene were less likely to develop Alzheimer's than those with the C-allele. Alleles are those genetic markers – A, C, G or T – that determine such inherited traits as eye and hair color, or susceptibility to disease.
"We are now beginning to dig deeper regarding the genetic sequence of KIBRA in individuals carrying, and not carrying, the T-allele. We believe this variation causes a potential lifelong difference in the total levels of KIBRA in the brain, and that this may influence one's risk for Alzheimer's," said Huentelman, who led a team that worked with several Arizona institutions, as well as other national and international universities and research institutions.
Dr. Eric Reiman, clinical director of TGen's Neurogenomics Division and executive director of the Banner Alzheimer's Institute, said, "This study suggests a link between the inherited genes involved in normal human memory and the predisposition to Alzheimer's disease."
"It provides promising new targets at which to aim new treatments to stave off Alzheimer's and improve memory," said Reiman, who also is director of the Arizona Alzheimer's Consortium and a contributor to the study.
The findings announced today are built on a 2006 study led by collaborative teams from Arizona and Zurich, Switzerland, and published in the journal Science. That pioneering TGen research revealed a link between KIBRA and memory, in which healthy adults with the KIBRA T-allele performed better on memory tests than those without this gene.
In the most recent analysis, Huentelman's team confirmed a link between KIBRA and Alzheimer's in three different ways:
Using TGen's powerful analytic tools to find a genetic association between the KIBRA gene and Alzheimer's disease, comparing more than 1,700 living and deceased people, with and without the disorder.
Using gene expression tools to find that KIBRA, and genes for other molecules that interact with KIBRA, were significantly altered in the neurons of people who had Alzheimer's disease, but not in individuals without the disorder.
Using a brain imaging technique called positron emission tomography (PET) to find that cognitively-normal, late-middle-aged people lacking the protective T-allele gene had reduced activity in parts of the brain usually affected by Alzheimer's.
Genetic association studyIn a study of 702 deceased persons diagnosed with Alzheimer's, and 1,026 living and deceased persons with and without Alzheimer's, researchers found that non-carriers of the KIBRA T-allele had increased risk of late-onset Alzheimer's.
The genotyped samples came from five centers, including three European organizations representing German, Dutch and Norwegian populations.
Gene expression studyThe gene expression study examined tissues from six regions of the brain among 47 deceased individuals. The brain tissue samples were provided by three Alzheimer's disease centers: Washington University in St. Louis, Mo.; Duke University in Durham, N.C.; and Sun Health Research Institute in Sun City, Ariz.
KIBRA, and a subset of other molecules directly interacting with it, were significantly altered in regions of the brain involved in Alzheimer's disease pathology. The regions investigated included the hippocampus, entorhinal cortex, posterior cingulate cortex, middle temporal gyrus, and superior frontal gyrus. However, they were not altered in a region of the brain typically unaffected by the disease -- the primary visual cortex.
Positron Emission Tomography scans
PET scans of 67 non-carriers of the KIBRA T-allele, and 69 carriers -- all with close relatives diagnosed with Alzheimer's -- showed that non-carriers exhibited, on average, similar alterations in the metabolic activity of key brain regions known to be altered in the earliest stages of the disease. All 136 individuals were mentally-normal, late-middle-aged Phoenix-area volunteers solicited from newspaper advertisements. They ranged in age from 47 to 68, with an average age of 55.
Scans showed that individuals without the KIBRA T-allele -- those with only KIBRA C-alleles from their mother and from their father -- had less metabolic brain activity when compared to those individuals carrying the T-allele -- from either their mother or father, or both. These differences were found in the precuneus and posterior cingulated regions of the brain affected in the earliest stages of Alzheimer's.
Previous work led by Reiman illustrated a similar finding when individuals were grouped according to whether they carried the most powerful genetic indicator for Alzheimer's -- the epsilon 4 allele of apolipoprotein E. In the current study, the effects of this allele were controlled for, yet similar observations were made. This suggests that KIBRA may play a role in a convergent biological risk pathway for the disease.
###
ParticipantsTGen's Jason Corneveaux and Dr. Winnie S. Liang were the paper's first authors.
Other Arizona participants in the study were: Arizona Alzheimer's Consortium, Banner Alzheimer's Institute, Sun Health Research Institute, St. Joseph's Hospital, Arizona State University, Mayo Clinic Arizona, and the University of Arizona's departments of Psychiatry, Radiology, and its Evelyn F. McKnight Brain Institute.
Other U.S. participants included: University of Miami, the National Institute on Aging, and the Mayo Clinic Rochester.
International collaborators included: the Netherlands Institute for Neurosciences, Netherlands; the Norwegian University of Science and Technology, and St. Olav's Hospital, Norway; the University of Bonn, Germany; and the University of Basel, Switzerland.
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