Even with devastating brain diseases such as Alzheimer's and Parkinson's, doctors can reach into their medical bags to find something to help a patient.
But they come up empty-handed when they try to help the vast majority of patients with ataxia - disabling disorders that rob people of their balance and coordination.
University of Florida neurologists are trying to change that with the help of a $1 million Challenge grant from the National Institute of Neurological Disorders and Stroke to establish a nationwide network of physician-scientists with expertise in clinical ataxia research.
"A lot of times I explain to patients the symptoms of ataxia are similar to what happens when someone gets too much alcohol into their system," says S.H. Subramony, M.D., a professor of neurology in the UF College of Medicine. "In either case there is slurred speech, inability to walk straight, falling, blurry vision - symptoms that indicate damage to a part of the brain called the cerebellum."
Ataxia - from the Greek "a taxis," meaning without order or coordination - can leave a patient unable to coordinate their eye blinks, let alone move. It can be hereditary or it could be brought on by strokes, tumors or other medical problems. One form, called sporadic ataxia, appears without apparent explanation in adults with no family history of the disease.
"Our first goal is to find a treatment to make patients' lives easier," said Tetsuo Ashizawa, M.D., chairman of the UF department of neurology and principal investigator and leader of the national effort, called the Clinical Research Consortium for Spinocerebellar Ataxias. "But the common thread ataxia shares with diseases such as Alzheimer's, Parkinson's, Huntington's and ALS is that neurons are dying. By studying ataxia, we can create insight into the neurodegenerative process in all of those diseases."
With laboratory and clinical research expertise from Ashizawa, Subramony and Michael Waters, M.D., Ph.D., director of the neurology department's stroke program, UF will lead nine other consortium institutions, including the Johns Hopkins University and Harvard University. The institutions are strategically placed across the nation so patients who have difficulty traveling can find close and state-of-the-art health care.
The ataxia consortium is part of the NIH's Rare Diseases Clinical Research Network, which will be awarding more than $117 million over the next five years to explore the natural history, epidemiology, diagnosis and treatment of more than 95 rare diseases.
By definition, a rare disease affects fewer than 200,000 persons in the United States. But put them all together - 6,500 rare diseases have been identified - and an estimated 25 million Americans are affected. Diabetes, in comparison, affects an estimated 24 million people.
"Collectively rare diseases can become very huge public health problem even though the reach of each individual disease is small," Ashizawa said. "I think the NIH recognized the need to provide outreach and medical care to patients, in addition to the need for research. Now we have a huge responsibility to achieve our goals for the taxpayers."
UF researchers will be working with cell cultures, animal models and patient samples to find targets to alleviate ataxia problems. In the meantime, scientists will build a natural history database to bring this devastating disease into more precise focus.
"We want to know how a patient will progress from day to day and hour to hour if they have degenerative ataxia disorders," Ashizawa said. "We want to know what factors worsen or improve the condition. For example, when patients are calm, they seem to do better. When they're upset and rushed, they do terribly. If they drink alcohol, they are much worse."
Creating or finding a drug that would help these patients is one of the consortium's goals. Ashizawa notes that it may be possible that deep brain stimulation surgery, a technique UF has expertise in that uses tiny electrical pulses to influence movement or moods, may be beneficial.
The first step is to identify the patients and create a nationwide registry funded by the NIH and the National Ataxia Foundation. In addition, the consortium is collaborating with ataxia groups in Europe, South America and Japan.
"Collaboration is a critical element of rare diseases research and the partnerships represented in this program have tremendous potential to make great strides in understanding these diseases," according to a statement by Stephen C. Groft, Pharm.D., director of NIH's Office of Rare Diseases Research. "The network emphasizes collaboration not just among investigators from multiple research sites but between investigators and patient advocates as well."
Challenge grants are part of the American Recovery and Reinvestment Initiative and address specific scientific and health research challenges that will benefit from two-year jumpstart funds.
Source
The University of Florida Health Science Center
воскресенье, 31 июля 2011 г.
четверг, 28 июля 2011 г.
New Guide Strives To Improve Care Of Neurological Conditions, UK
A ground-breaking guide aimed at promoting the benefits of specialist nurses in the care of people with long term neurological conditions is launched today.
The important document results from a unique partnership between three of the UK's leading charities for neurological conditions, the MS Society, Epilepsy Action and the Parkinson's Disease Society, with the Department of Health, Royal College of Nursing and NHS National Workforce Projects.
The guide, Long Term Neurological Conditions . A Good Practice Guide to the Development of the Multidisciplinary Team and the Value of the Specialist Nurse, will be launched at the Harrogate International Conference Centre.
The guidance document is being launched exactly one year on from a specialist nursing summit held on 1 May 2007 with Ivan Lewis, Minister for Care Services. This highlighted the vital role of specialist nurses in helping people with multiple sclerosis (MS), epilepsy and Parkinson's disease. The outcome of the meeting was that a guidance document would be prepared to outline best practice and educate health commissioners on the benefits of protecting the specialist nurse post.
It is aimed at commissioners and service providers for people with long term neurological conditions to help them offer the right service, delivered by an appropriate workforce, to meet patients' needs. It outlines why services for neurological conditions are important, demonstrates the value of multi-disciplinary teams and clarifies the contribution of specialist nurses. For example:
- An MS nurse could save an average PCT up to ??18,000 a year by treating relapses at home rather than in hospital
- Misdiagnosis of epilepsy in England cost ??134 million in 2004. An epilepsy nurse can save ??184 per patient per year by improving diagnosis - a major saving across a primary care trust (PCT) with, on average, more than 80 epilepsy patients
- More than one in three people with Parkinson's disease are admitted to hospital every year. A Parkinson's disease nurse can have a significant impact in reducing hospital admissions and length of stay, addressing inequalities in access to neurologists ensuring specialist care is delivered and improving overall care and treatment.
Ann Keen MP, Minister for Health Services, said: "This guide is bound to become invaluable for service managers, staff and commissioners aspiring to excellence in the treatment of long term conditions. It shows that being able to deliver effective care does not necessarily mean spending more money but ensuring that the best methods of teamwork, planning and treatment are in place."
The MS Society funds more than 100 of the UK's MS specialist nurses and worked with the UK MS Specialist Nurses Association to contribute to the guide.
MS Society chief executive Simon Gillespie said: "The support of an MS nurse can make a massive difference to someone living with this devastating condition. Their range of knowledge and expertise is unique. This guide is an important step forward in safeguarding existing nurses and in making the case for more."
Epilepsy Action has been funding epilepsy specialist nurses (ESNs) through its Sapphire Nurse Scheme since 1995. There are currently approximately 200 ESNs in England; 80 of which are Sapphire Nurses.
Epilepsy Action chief executive Phil Lee said: "We are delighted to have been able to play an important part in producing this guide. It is a very positive step forward for people with epilepsy in that it will hopefully lead to more epilepsy specialist nurses. This in turn would go towards improving care."
The Parkinson's Disease Society has invested more than ??8m in specialist Parkinson's nursing services since 1994 and there are currently more than 230 of them working across the UK.
Steve Ford, chief executive of the Parkinson's Disease Society, said: "Access to a Parkinson's disease nurse specialist is the number one campaign priority for people with Parkinson's. These nurses not only ensure patients are able to manage their symptoms effectively, they also offer the local health organisations opportunities to innovate how care is delivered."
The document can be viewed here.
Health Care Workforce
The important document results from a unique partnership between three of the UK's leading charities for neurological conditions, the MS Society, Epilepsy Action and the Parkinson's Disease Society, with the Department of Health, Royal College of Nursing and NHS National Workforce Projects.
The guide, Long Term Neurological Conditions . A Good Practice Guide to the Development of the Multidisciplinary Team and the Value of the Specialist Nurse, will be launched at the Harrogate International Conference Centre.
The guidance document is being launched exactly one year on from a specialist nursing summit held on 1 May 2007 with Ivan Lewis, Minister for Care Services. This highlighted the vital role of specialist nurses in helping people with multiple sclerosis (MS), epilepsy and Parkinson's disease. The outcome of the meeting was that a guidance document would be prepared to outline best practice and educate health commissioners on the benefits of protecting the specialist nurse post.
It is aimed at commissioners and service providers for people with long term neurological conditions to help them offer the right service, delivered by an appropriate workforce, to meet patients' needs. It outlines why services for neurological conditions are important, demonstrates the value of multi-disciplinary teams and clarifies the contribution of specialist nurses. For example:
- An MS nurse could save an average PCT up to ??18,000 a year by treating relapses at home rather than in hospital
- Misdiagnosis of epilepsy in England cost ??134 million in 2004. An epilepsy nurse can save ??184 per patient per year by improving diagnosis - a major saving across a primary care trust (PCT) with, on average, more than 80 epilepsy patients
- More than one in three people with Parkinson's disease are admitted to hospital every year. A Parkinson's disease nurse can have a significant impact in reducing hospital admissions and length of stay, addressing inequalities in access to neurologists ensuring specialist care is delivered and improving overall care and treatment.
Ann Keen MP, Minister for Health Services, said: "This guide is bound to become invaluable for service managers, staff and commissioners aspiring to excellence in the treatment of long term conditions. It shows that being able to deliver effective care does not necessarily mean spending more money but ensuring that the best methods of teamwork, planning and treatment are in place."
The MS Society funds more than 100 of the UK's MS specialist nurses and worked with the UK MS Specialist Nurses Association to contribute to the guide.
MS Society chief executive Simon Gillespie said: "The support of an MS nurse can make a massive difference to someone living with this devastating condition. Their range of knowledge and expertise is unique. This guide is an important step forward in safeguarding existing nurses and in making the case for more."
Epilepsy Action has been funding epilepsy specialist nurses (ESNs) through its Sapphire Nurse Scheme since 1995. There are currently approximately 200 ESNs in England; 80 of which are Sapphire Nurses.
Epilepsy Action chief executive Phil Lee said: "We are delighted to have been able to play an important part in producing this guide. It is a very positive step forward for people with epilepsy in that it will hopefully lead to more epilepsy specialist nurses. This in turn would go towards improving care."
The Parkinson's Disease Society has invested more than ??8m in specialist Parkinson's nursing services since 1994 and there are currently more than 230 of them working across the UK.
Steve Ford, chief executive of the Parkinson's Disease Society, said: "Access to a Parkinson's disease nurse specialist is the number one campaign priority for people with Parkinson's. These nurses not only ensure patients are able to manage their symptoms effectively, they also offer the local health organisations opportunities to innovate how care is delivered."
The document can be viewed here.
Health Care Workforce
понедельник, 25 июля 2011 г.
Nina Hossain Braves The Snow For Alzheimer's Charities At The Bupa Great Winter Run, UK
Despite sub-zero temperatures and a four-inch snowfall, ITV newsreader, journalist and presenter Nina Hossain took part in the Bupa Great Winter Run in Edinburgh on 8 January for Alzheimer's Society.
The 5k course was slightly amended to take account of the adverse weather conditions and Nina crossed the line safely in 38:47. Nina was the official starter for the run along with former long and middle distance runner and Olympic medallist Liz McColgan.
Alzheimer's Society supporter Nina, said,
'At the beginning of a Bupa Great Run, I always feel quite emotional. I hated sport at school, so to be actually taking part feels like an achievement in itself. It's been a great day and wonderful to see so many people running for Bupa's nominated charities, Alzheimer's Society and Alzheimer Scotland. By taking part in a Bupa Great Run for these charities, you really can improve the lives of people with dementia and their carers.'
This is the third consecutive year that Bupa has chosen Alzheimer's Society and Alzheimer Scotland as its nominated charities for the Bupa Great Run Series. Over 10,000 people have run for the two charities in the Bupa Great Run Series since the beginning of the partnership and, by the end of 2011, the charities hope to have raised in excess of ??3.5 million.
Source:
Alzheimer's Society
The 5k course was slightly amended to take account of the adverse weather conditions and Nina crossed the line safely in 38:47. Nina was the official starter for the run along with former long and middle distance runner and Olympic medallist Liz McColgan.
Alzheimer's Society supporter Nina, said,
'At the beginning of a Bupa Great Run, I always feel quite emotional. I hated sport at school, so to be actually taking part feels like an achievement in itself. It's been a great day and wonderful to see so many people running for Bupa's nominated charities, Alzheimer's Society and Alzheimer Scotland. By taking part in a Bupa Great Run for these charities, you really can improve the lives of people with dementia and their carers.'
This is the third consecutive year that Bupa has chosen Alzheimer's Society and Alzheimer Scotland as its nominated charities for the Bupa Great Run Series. Over 10,000 people have run for the two charities in the Bupa Great Run Series since the beginning of the partnership and, by the end of 2011, the charities hope to have raised in excess of ??3.5 million.
Source:
Alzheimer's Society
пятница, 22 июля 2011 г.
Scientists ID Possible Biomarker To Gauge Alzheimer's Prognosis, Effect Of Therapies
UCLA researchers have identified a new biomarker that could help them track how effectively the immune system is able to clear the brain of amyloid beta, which forms the plaques considered one of the hallmarks of Alzheimer's disease.
The pilot study, currently published online in the Journal of Alzheimer's Disease, demonstrates how the immune gene MGAT3, which is essential in clearing amyloid beta, is expressed differently in different Alzheimer's patients. The finding may be useful in providing more highly individualized disease prognoses in the future.
It may also help researchers understand which patients will respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, both of which were shown in previous studies by this UCLA research team to help stimulate specific immune system cells to clear amyloid beta in a laboratory test.
Genes hold instructions to create proteins that determine all bodily processes, from moving blood through the veins to stimulating the immune system. The genome of each cell, which is made up of hereditary information, sends out messages to "turn on" various genes according to actual needs.
In earlier research, the UCLA team showed that Alzheimer's patients may have a defect in messaging from the MGAT3 gene, which could help explain why this population cannot effectively clear amyloid beta.
In the current study, researchers used a blood-based biomarker to identify three abnormal ways of processing MGAT3 gene information, which could lead to different disease prognoses.
"Alzheimer's disease robs a person of identity and is a huge burden for families, caregivers and society," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System. "This is one of the first studies demonstrating the role of the immune system in helping track Alzheimer's disease prognosis and the impact of therapies."
For the study, scientists drew blood samples from 20 Alzheimer's disease patients and 20 healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.
They incubated the immune cells overnight with amyloid beta to test the cells' ability to "turn on" MGAT3. They also added a synthetic form of curcumin to some of the cells to gauge the effect it had on MGAT3 expression and the absorption of amyloid beta.
Based on the results, the researchers identified three groups of Alzheimer's patients.
Type 0 patients: This group had very low expression of MGAT3 and very low absorption rates of amyloid beta.
Type I patients: This group also had low expression of MGAT3 and low amyloid beta absorption rates, but the strength of the MGAT3 message and the absorption of amyloid beta increased when researchers stimulated the macrophages with synthetic curcumin.
Type II patients: This group initially had high amyloid beta absorption rates, but when scientists added synthetic curcumin, MGAT3 expression lessened and absorption was reduced.
In addition, researchers found that for Type I and Type II patients, the clearing of amyloid beta was dependent on vitamin D3, a type of vitamin D that occurs naturally in these cells. When they blocked vitamin D3 use by the macrophages in the laboratory, they found that absorption of amyloid beta suffered.
"These findings demonstrate three very different levels of immunity and possible reactions to natural therapies of vitamin D3 and curcumin," Fiala said. "These differences could point to a new way to track the progression of Alzheimer's disease and the effectiveness of these natural therapies based on an individual patient's immunity."
Fourteen of the 20 Alzheimer's disease patients have been followed for two years, and researchers noted that those who were Type 0 had a worse two-year prognosis regarding the loss of their ability to live independently than the other two types of patients.
Fiala said that 45 percent of the Alzheimer's patients in the study were Type 0 in their MGAT3 immunity expression, while only 10 percent of the healthy controls fell into this patient type. The effects of vitamin D3 and curcumin have not yet been adequately investigated in Type 0 patients.
The healthy control group, made up of university professors, business people and Alzheimer's caregivers, displayed varying results in their ability to absorb amyloid beta. Overall, the university professors demonstrated good to excellent absorption of amyloid beta, and the caregivers displayed lower absorption rates. Fiala notes that the stress of caring for Alzheimer's patients may also affect the caregivers' immunity.
Fiala added that a larger clinical trial needs to be completed to validate findings from this pilot study. He said that while vitamin D3 seems to be helpful to most people, the benefits of synthetic curcumin are more individualized, depending on the patient. In the future, a commercially available test may be able to check for MGAT3 immunity.
During the study, researchers also noted that one Type II patient who underwent hip surgery experienced temporary cognitive dysfunction related to the general surgery anesthesia, which is a phenomenon that can occur. Researchers checked the patient's MGAT3 immunity and found that the patient's ability to clear amyloid beta had declined after surgery but improved in later months, along with cognitive function, possibly due to the vitamin D3 supplementation the patient had undertaken - although this was not a part of the study.
According to Fiala, this might be an example of how vitamin D3 may help improve amyloid beta clearance. He noted that this is early laboratory research and that no dosage of vitamin D or curcumin can be recommended at this time. Larger studies with more patients are planned.
The study was funded by the Alzheimer's Association.
Additional authors include Michelle Mahanian, Mark Rosenthal, Eric Tse, Tiffany Cho and Rachel Weitzman, Department of Medicine, Greater Los Angeles VA Medical Center and David Geffen School of Medicine at UCLA; Matthew T. Mizwicki, Department of Biochemistry, University of California, Riverside; James Sayre, Department of Biostatistics, University of California School of Public Health, Los Angeles and Verna Porter, Department of Neurology, David Geffen School of Medicine at UCLA.
Source:
University of California, Los Angeles (UCLA), Health Sciences
The pilot study, currently published online in the Journal of Alzheimer's Disease, demonstrates how the immune gene MGAT3, which is essential in clearing amyloid beta, is expressed differently in different Alzheimer's patients. The finding may be useful in providing more highly individualized disease prognoses in the future.
It may also help researchers understand which patients will respond to therapy with vitamin D3 and curcumin, a chemical found in turmeric spice, both of which were shown in previous studies by this UCLA research team to help stimulate specific immune system cells to clear amyloid beta in a laboratory test.
Genes hold instructions to create proteins that determine all bodily processes, from moving blood through the veins to stimulating the immune system. The genome of each cell, which is made up of hereditary information, sends out messages to "turn on" various genes according to actual needs.
In earlier research, the UCLA team showed that Alzheimer's patients may have a defect in messaging from the MGAT3 gene, which could help explain why this population cannot effectively clear amyloid beta.
In the current study, researchers used a blood-based biomarker to identify three abnormal ways of processing MGAT3 gene information, which could lead to different disease prognoses.
"Alzheimer's disease robs a person of identity and is a huge burden for families, caregivers and society," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA and the Veterans Affairs Greater Los Angeles Healthcare System. "This is one of the first studies demonstrating the role of the immune system in helping track Alzheimer's disease prognosis and the impact of therapies."
For the study, scientists drew blood samples from 20 Alzheimer's disease patients and 20 healthy controls and then isolated critical immune cells from the blood called macrophages, which are responsible for gobbling up amyloid beta and other waste products in the brain and body.
They incubated the immune cells overnight with amyloid beta to test the cells' ability to "turn on" MGAT3. They also added a synthetic form of curcumin to some of the cells to gauge the effect it had on MGAT3 expression and the absorption of amyloid beta.
Based on the results, the researchers identified three groups of Alzheimer's patients.
Type 0 patients: This group had very low expression of MGAT3 and very low absorption rates of amyloid beta.
Type I patients: This group also had low expression of MGAT3 and low amyloid beta absorption rates, but the strength of the MGAT3 message and the absorption of amyloid beta increased when researchers stimulated the macrophages with synthetic curcumin.
Type II patients: This group initially had high amyloid beta absorption rates, but when scientists added synthetic curcumin, MGAT3 expression lessened and absorption was reduced.
In addition, researchers found that for Type I and Type II patients, the clearing of amyloid beta was dependent on vitamin D3, a type of vitamin D that occurs naturally in these cells. When they blocked vitamin D3 use by the macrophages in the laboratory, they found that absorption of amyloid beta suffered.
"These findings demonstrate three very different levels of immunity and possible reactions to natural therapies of vitamin D3 and curcumin," Fiala said. "These differences could point to a new way to track the progression of Alzheimer's disease and the effectiveness of these natural therapies based on an individual patient's immunity."
Fourteen of the 20 Alzheimer's disease patients have been followed for two years, and researchers noted that those who were Type 0 had a worse two-year prognosis regarding the loss of their ability to live independently than the other two types of patients.
Fiala said that 45 percent of the Alzheimer's patients in the study were Type 0 in their MGAT3 immunity expression, while only 10 percent of the healthy controls fell into this patient type. The effects of vitamin D3 and curcumin have not yet been adequately investigated in Type 0 patients.
The healthy control group, made up of university professors, business people and Alzheimer's caregivers, displayed varying results in their ability to absorb amyloid beta. Overall, the university professors demonstrated good to excellent absorption of amyloid beta, and the caregivers displayed lower absorption rates. Fiala notes that the stress of caring for Alzheimer's patients may also affect the caregivers' immunity.
Fiala added that a larger clinical trial needs to be completed to validate findings from this pilot study. He said that while vitamin D3 seems to be helpful to most people, the benefits of synthetic curcumin are more individualized, depending on the patient. In the future, a commercially available test may be able to check for MGAT3 immunity.
During the study, researchers also noted that one Type II patient who underwent hip surgery experienced temporary cognitive dysfunction related to the general surgery anesthesia, which is a phenomenon that can occur. Researchers checked the patient's MGAT3 immunity and found that the patient's ability to clear amyloid beta had declined after surgery but improved in later months, along with cognitive function, possibly due to the vitamin D3 supplementation the patient had undertaken - although this was not a part of the study.
According to Fiala, this might be an example of how vitamin D3 may help improve amyloid beta clearance. He noted that this is early laboratory research and that no dosage of vitamin D or curcumin can be recommended at this time. Larger studies with more patients are planned.
The study was funded by the Alzheimer's Association.
Additional authors include Michelle Mahanian, Mark Rosenthal, Eric Tse, Tiffany Cho and Rachel Weitzman, Department of Medicine, Greater Los Angeles VA Medical Center and David Geffen School of Medicine at UCLA; Matthew T. Mizwicki, Department of Biochemistry, University of California, Riverside; James Sayre, Department of Biostatistics, University of California School of Public Health, Los Angeles and Verna Porter, Department of Neurology, David Geffen School of Medicine at UCLA.
Source:
University of California, Los Angeles (UCLA), Health Sciences
вторник, 19 июля 2011 г.
Multifaceted Aspects Of AD Explored In Journal Of Alzheimer's Disease Special Issue
A recently published special issue of the Journal of Alzheimer's Disease contains the contributions from experts in the field of aging, dementia and Alzheimer's disease, who attended the "Fourth Annual Meeting on Brain aging and Dementia: From successful aging to severe dementia." Held in Perugia under the auspices of the Italian Psychogeriatric Association, a member of the International Psychogeriatric Association, the meeting celebrated the centenary of Alzheimer's first description of the disease.
The articles cover several topics on AD: sociological, epidemiological, clinical and biological aspects offer a wide overview on this multifaceted disease.
Robert Binstock, from Case Western Reserve University, Cleveland (USA), reports some reflections on the ethical, moral and policy challenges for healthcare professionals and politicians due to the aging of industrialized nations. This social phenomenon is associated with an enhanced demand for both acute and long-term healthcare for the elderly that will increasingly strain economic resources.
Laura Fratiglioni and Hui-Xin Wang, from the Karolinska Institute of Stockholm (Sweden), review the concept of "brain reserve" that refers to the ability to tolerate the age-related changes and disease-related pathology in the brain without developing clear clinical symptoms. Epidemiological studies indicate that brain reserve is related to a number of aspects including high education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle.
Guest Editor Patrizia Mecocci and colleagues from the Italian University of Perugia (Elena Mariani) and University of Palermo (Roberto Monastero) review the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of Mild Cognitive Impairment, a nosological entity proposed as an intermediate state between normal aging and dementia, with specific attention to possible markers of conversion to dementia.
Ezio Giacobini and Robert Becker from the University of Geneva (Switzerland) expand on possible treatments of AD that should modify the course of the pathological processes at the basis of this disease. Several active and passive vaccines against amyloid-?? humanized antibody, drugs aiming to reduce tau phosphorylation (GSK3 inhibitors), anti-amyloid-aggregation and anti-APO-E molecules are considered, while the developments of gamma-and beta-secretase inhibitors, due to intrinsic difficulties, seem to have not yet reached the clinical stages.
Clive Ballard and his colleagues Susanne Sorensen and Samantha Sharp from King's College, London (UK) give a brief overview of the clinical effectiveness of cholinesterase inhibitors for the treatment of Alzheimer's disease, discuss in detail the NICE appraisal of these treatments in the UK as a example of an attempt at a standardized evaluation of cost-effectiveness and argue a proposed way forward to achieve a unified and consistent approach to the assessment of cost-effectiveness for anti-dementia therapies.
Allan Butterfield and Rukhsana Sultana from the University of Kentucky, Lexington (USA) write of their studies on oxidative stress in AD and MCI brain indexed by protein oxidation and lipid peroxidation and summarize findings of oxidatively modified proteins using redox proteomics approach in AD and MCI brain aimed to investigate the mechanism that may be involved in their pathogenesis as well as in terms of MCI progression to AD.
Alessandro Serretti, Paolo Olgiati and Diana De Ronchi, from the University of Bologna (Italy) discuss the genetics of Alzheimer's disease, focusing on the sporadic form in which most genes, related to the amyloid-?? deposition, oxidative stress and inflammatory response are involved. They report that genetic mechanisms are also involved in expression of depression and psychotic symptoms that occur in a large proportion of AD patients and in the therapeutic effect of drugs currently used.
Cristina Lanni and colleagues from the University of Pavia (Italy) discuss the methodologies that have been used to identify an altered conformational status of p53 in fibroblasts of AD patients. They explain that this alteration may be related to exposure to low amounts of soluble A?? peptide, not resulting in cytotoxic effects. On this basis, they hypothesize that unfolded p53 could be considered as an agent participating in the early pathogenesis and as a specific marker of the early stage of AD.
Finally, Eugenio Mocchegiani and Marco Malavolta from INRCA (National Institute of Research and Cure for the Elderly) of Ancona (Italy) write about the role of zinc homeostasis in different conditions of brain dysfunction, including brain inflammatory status, aging brain and neurodegeneration They also discuss the role played by metallothioneins (which regulate the intracellular free zinc ions) and ??2 macroglobulin (a zinc-binding protein) in aging and AD.
Special Issue "The Multifaceted Aspects of Alzheimer's Disease: From Social to Molecular Problems" (Guest Editor: Patrizia Mecocci), Journal of Alzheimer's Disease, Volume 12, Issue 1 (2007)
Source: Astrid Engelen
IOS Press
The articles cover several topics on AD: sociological, epidemiological, clinical and biological aspects offer a wide overview on this multifaceted disease.
Robert Binstock, from Case Western Reserve University, Cleveland (USA), reports some reflections on the ethical, moral and policy challenges for healthcare professionals and politicians due to the aging of industrialized nations. This social phenomenon is associated with an enhanced demand for both acute and long-term healthcare for the elderly that will increasingly strain economic resources.
Laura Fratiglioni and Hui-Xin Wang, from the Karolinska Institute of Stockholm (Sweden), review the concept of "brain reserve" that refers to the ability to tolerate the age-related changes and disease-related pathology in the brain without developing clear clinical symptoms. Epidemiological studies indicate that brain reserve is related to a number of aspects including high education, adult-life occupational work complexity, as well as a mentally and socially integrated lifestyle.
Guest Editor Patrizia Mecocci and colleagues from the Italian University of Perugia (Elena Mariani) and University of Palermo (Roberto Monastero) review the most recent aspects related to the epidemiological, clinical, neuropathological, neuroimaging, biochemical and therapeutic aspects of Mild Cognitive Impairment, a nosological entity proposed as an intermediate state between normal aging and dementia, with specific attention to possible markers of conversion to dementia.
Ezio Giacobini and Robert Becker from the University of Geneva (Switzerland) expand on possible treatments of AD that should modify the course of the pathological processes at the basis of this disease. Several active and passive vaccines against amyloid-?? humanized antibody, drugs aiming to reduce tau phosphorylation (GSK3 inhibitors), anti-amyloid-aggregation and anti-APO-E molecules are considered, while the developments of gamma-and beta-secretase inhibitors, due to intrinsic difficulties, seem to have not yet reached the clinical stages.
Clive Ballard and his colleagues Susanne Sorensen and Samantha Sharp from King's College, London (UK) give a brief overview of the clinical effectiveness of cholinesterase inhibitors for the treatment of Alzheimer's disease, discuss in detail the NICE appraisal of these treatments in the UK as a example of an attempt at a standardized evaluation of cost-effectiveness and argue a proposed way forward to achieve a unified and consistent approach to the assessment of cost-effectiveness for anti-dementia therapies.
Allan Butterfield and Rukhsana Sultana from the University of Kentucky, Lexington (USA) write of their studies on oxidative stress in AD and MCI brain indexed by protein oxidation and lipid peroxidation and summarize findings of oxidatively modified proteins using redox proteomics approach in AD and MCI brain aimed to investigate the mechanism that may be involved in their pathogenesis as well as in terms of MCI progression to AD.
Alessandro Serretti, Paolo Olgiati and Diana De Ronchi, from the University of Bologna (Italy) discuss the genetics of Alzheimer's disease, focusing on the sporadic form in which most genes, related to the amyloid-?? deposition, oxidative stress and inflammatory response are involved. They report that genetic mechanisms are also involved in expression of depression and psychotic symptoms that occur in a large proportion of AD patients and in the therapeutic effect of drugs currently used.
Cristina Lanni and colleagues from the University of Pavia (Italy) discuss the methodologies that have been used to identify an altered conformational status of p53 in fibroblasts of AD patients. They explain that this alteration may be related to exposure to low amounts of soluble A?? peptide, not resulting in cytotoxic effects. On this basis, they hypothesize that unfolded p53 could be considered as an agent participating in the early pathogenesis and as a specific marker of the early stage of AD.
Finally, Eugenio Mocchegiani and Marco Malavolta from INRCA (National Institute of Research and Cure for the Elderly) of Ancona (Italy) write about the role of zinc homeostasis in different conditions of brain dysfunction, including brain inflammatory status, aging brain and neurodegeneration They also discuss the role played by metallothioneins (which regulate the intracellular free zinc ions) and ??2 macroglobulin (a zinc-binding protein) in aging and AD.
Special Issue "The Multifaceted Aspects of Alzheimer's Disease: From Social to Molecular Problems" (Guest Editor: Patrizia Mecocci), Journal of Alzheimer's Disease, Volume 12, Issue 1 (2007)
Source: Astrid Engelen
IOS Press
суббота, 16 июля 2011 г.
Supercomputer Simulations May Pinpoint Causes Of Parkinson's, Alzheimer's Diseases
Using the massive computer-simulation power of the San Diego Supercomputer Center (SDSC) at UC San Diego, researchers are zeroing in on the causes of Parkinson's disease, Alzheimer's disease, rheumatoid arthritis and other diseases.
A study published in Federation of European Biochemical Societies (FEBS) Journal offers - for the first time - a model for the complex process of aggregation of a protein known as alpha-synuclein, which in turn leads to harmful ring-like or pore-like structures in human membranes, the kind of damage found in Parkinson's and Alzheimer's patients.
The researchers at SDSC and UC San Diego also found that the destructive properties of alpha-synuclein can be blocked by beta-synuclein - a finding that could lead to treatments for many debilitating diseases.
The current journal's cover features an image from the research that helps illustrate the scientists' work.
"This is one of the first studies to use supercomputers to model how alpha-synuclein complexes damage the cells, and how that could be blocked," said Eliezer Masliah, professor of neurosciences and pathology at UC San Diego. "We believe that these ring- or pore-like structures might be deleterious to the cells, and we have a unique opportunity to better understand how alpha-synuclein is involved in the pathogenesis of Parkinson's disease, and how to reverse this process."
Igor Tsigelny, project scientist in chemistry and biochemistry at UC San Diego and a researcher at SDSC, said that the team's research helped confirm what researchers had suspected. "The present study - using molecular modeling and molecular dynamics simulations in combination with biochemical and ultrastructural analysis - shows that alpha-synuclein can lead to the formation of pore-like structures on membranes."
In contrast, he said, "beta-synuclein appears to block the propagation of alpha-synucleins into harmful structures."
The complex calculations for the study were performed on Blue Gene supercomputers at SDSC and the Argonne National Labs.
Tsigelny worked in collaboration with Pazit Bar-On, Department of Neurosciences; Yuriy Sharikov of SDSC; Leslie Crews of the Department of Pathology; Makoto Hashimoto of Neurosciences; Mark A. Miller of SDSC; Steve H. Keller in Medicine; Oleksandr Platoshyn and Jason X.J. Yuan, both in Medicine; and Masliah, all at UC San Diego.
The research was supported by funding from the National Institutes of Health, a Department of Energy INCITE Grant, the Argonne National Laboratory, and the SDSC/ IBM Institute for Innovation in Biomedical Simulations and Visualization.
Contact: Paul K. Mueller
University of California - San Diego
A study published in Federation of European Biochemical Societies (FEBS) Journal offers - for the first time - a model for the complex process of aggregation of a protein known as alpha-synuclein, which in turn leads to harmful ring-like or pore-like structures in human membranes, the kind of damage found in Parkinson's and Alzheimer's patients.
The researchers at SDSC and UC San Diego also found that the destructive properties of alpha-synuclein can be blocked by beta-synuclein - a finding that could lead to treatments for many debilitating diseases.
The current journal's cover features an image from the research that helps illustrate the scientists' work.
"This is one of the first studies to use supercomputers to model how alpha-synuclein complexes damage the cells, and how that could be blocked," said Eliezer Masliah, professor of neurosciences and pathology at UC San Diego. "We believe that these ring- or pore-like structures might be deleterious to the cells, and we have a unique opportunity to better understand how alpha-synuclein is involved in the pathogenesis of Parkinson's disease, and how to reverse this process."
Igor Tsigelny, project scientist in chemistry and biochemistry at UC San Diego and a researcher at SDSC, said that the team's research helped confirm what researchers had suspected. "The present study - using molecular modeling and molecular dynamics simulations in combination with biochemical and ultrastructural analysis - shows that alpha-synuclein can lead to the formation of pore-like structures on membranes."
In contrast, he said, "beta-synuclein appears to block the propagation of alpha-synucleins into harmful structures."
The complex calculations for the study were performed on Blue Gene supercomputers at SDSC and the Argonne National Labs.
Tsigelny worked in collaboration with Pazit Bar-On, Department of Neurosciences; Yuriy Sharikov of SDSC; Leslie Crews of the Department of Pathology; Makoto Hashimoto of Neurosciences; Mark A. Miller of SDSC; Steve H. Keller in Medicine; Oleksandr Platoshyn and Jason X.J. Yuan, both in Medicine; and Masliah, all at UC San Diego.
The research was supported by funding from the National Institutes of Health, a Department of Energy INCITE Grant, the Argonne National Laboratory, and the SDSC/ IBM Institute for Innovation in Biomedical Simulations and Visualization.
Contact: Paul K. Mueller
University of California - San Diego
среда, 13 июля 2011 г.
Review: Exercise Not Proven As Dementia Treatment
Physical activity is a good thing for nearly everybody and clearly boosts alertness and a sense of well-being. So can we use it as a treatment for elderly patients with dementia? That's a good question, but existing research doesn't provide an answer, according to a new Cochrane Library review.
"Physical activity may be beneficial for persons with dementia. But due to the small number of studies we have not been able to demonstrate this," said review lead author Dorothy Forbes, an associate professor with the faculty of health sciences at the University of Western Ontario, in Canada.
On the other hand, there is no evidence that physical activity is harmful either, she said.
Estimates indicate that dementia known in the past as senility affects about 14 percent of Americans ages 71 and older. More than one-third of Americans over 90 likely suffer from the condition, which causes forgetfulness, confusion and muddled thinking. A variety of medical conditions causes dementia, including Alzheimer's disease and stroke.
Physicians are unlikely to prescribe physical activity as a treatment for dementia patients because there is little evidence to support its value, Forbes said. Nevertheless, exercise is not impossible for many dementia patients, who might be able to walk, swim and exercise in groups with assistance, she said.
Researchers have shown that exercise can improve cognition and mental health in older adults, and some studies suggest that it could delay dementia from three to six years or reduce the risk that patients will develop cognitive problems, Forbes said.
"It is less clear if physical activity manages or improves other symptoms among persons with a diagnosis of dementia," she said.
In the new review, Forbes and colleagues sought to shed some light on that issue.
The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
While evidence from animal research indicates that physical activity could be a useful treatment for dementia, the review authors only found four studies that examined the effects of exercise in humans.
Two of the studies were not included in the analysis because the reviewers could not get details from the original study authors.
Both of the remaining studies were small and only included Alzheimer disease patients. One looked at just 11 patients; the other examined 134, but many of those did not complete their exercise regimens.
Still, the researchers in the latter study found that those who did exercise seemed to do better at handling the tasks of daily living.
None of the studies looked at the effects on caregivers or on overall health-care costs.
Why have there been so few high-quality studies? Research into dementia is in its early stages, and largely has focused on diagnosis, assessment of severity and drug treatments, Forbes said.
To make things more challenging, funding is limited and it can be difficult to study people who might not be able to give consent or comply easily with the requirements of a study.
While there is little research supporting physical activity as a helpful treatment for elderly people with dementia, there is no evidence that it is harmful, Forbes said.
"Indeed, there is some suggestion that physical activity manages or improves function in persons with dementia," she said. "Further well-designed trials are necessary to demonstrate the effects of physical activity."
Dr. William Thies, vice president of medical and scientific relations for the Alzheimer's Association, agreed that the studies reviewed are not conclusive. "It's true that the studies had a trend toward benefits, but that's not enough to say that physical exercise ought to be a necessary element of everyone's dementia care."
Still, the review findings do not change the fact that exercise remains crucial to long-term health, he said. "The person who has built physical activity into their lifestyle is going to be in better health, more functional and probably happier over the long run," he said.
Health Behavior News Service
Center for the Advancement of Health 2000 Florida Ave. NW, Ste 210
Washington, DC 20009
United States
hbns
"Physical activity may be beneficial for persons with dementia. But due to the small number of studies we have not been able to demonstrate this," said review lead author Dorothy Forbes, an associate professor with the faculty of health sciences at the University of Western Ontario, in Canada.
On the other hand, there is no evidence that physical activity is harmful either, she said.
Estimates indicate that dementia known in the past as senility affects about 14 percent of Americans ages 71 and older. More than one-third of Americans over 90 likely suffer from the condition, which causes forgetfulness, confusion and muddled thinking. A variety of medical conditions causes dementia, including Alzheimer's disease and stroke.
Physicians are unlikely to prescribe physical activity as a treatment for dementia patients because there is little evidence to support its value, Forbes said. Nevertheless, exercise is not impossible for many dementia patients, who might be able to walk, swim and exercise in groups with assistance, she said.
Researchers have shown that exercise can improve cognition and mental health in older adults, and some studies suggest that it could delay dementia from three to six years or reduce the risk that patients will develop cognitive problems, Forbes said.
"It is less clear if physical activity manages or improves other symptoms among persons with a diagnosis of dementia," she said.
In the new review, Forbes and colleagues sought to shed some light on that issue.
The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.
While evidence from animal research indicates that physical activity could be a useful treatment for dementia, the review authors only found four studies that examined the effects of exercise in humans.
Two of the studies were not included in the analysis because the reviewers could not get details from the original study authors.
Both of the remaining studies were small and only included Alzheimer disease patients. One looked at just 11 patients; the other examined 134, but many of those did not complete their exercise regimens.
Still, the researchers in the latter study found that those who did exercise seemed to do better at handling the tasks of daily living.
None of the studies looked at the effects on caregivers or on overall health-care costs.
Why have there been so few high-quality studies? Research into dementia is in its early stages, and largely has focused on diagnosis, assessment of severity and drug treatments, Forbes said.
To make things more challenging, funding is limited and it can be difficult to study people who might not be able to give consent or comply easily with the requirements of a study.
While there is little research supporting physical activity as a helpful treatment for elderly people with dementia, there is no evidence that it is harmful, Forbes said.
"Indeed, there is some suggestion that physical activity manages or improves function in persons with dementia," she said. "Further well-designed trials are necessary to demonstrate the effects of physical activity."
Dr. William Thies, vice president of medical and scientific relations for the Alzheimer's Association, agreed that the studies reviewed are not conclusive. "It's true that the studies had a trend toward benefits, but that's not enough to say that physical exercise ought to be a necessary element of everyone's dementia care."
Still, the review findings do not change the fact that exercise remains crucial to long-term health, he said. "The person who has built physical activity into their lifestyle is going to be in better health, more functional and probably happier over the long run," he said.
Health Behavior News Service
Center for the Advancement of Health 2000 Florida Ave. NW, Ste 210
Washington, DC 20009
United States
hbns
воскресенье, 10 июля 2011 г.
The Pathways Of Alzheimer's That Strikes At The Young: Use Of Computational Model
Alzheimer's disease (AD) is a tragic disease that robs an individual of their memory and mental capacity. One in eight people over the age of 65 now suffer from the disease and one in two people over 85 are diagnosed with the disease. Contrary to popular belief, Alzheimer's does not only affect the elderly. Familial Alzheimer's disease (FAD), an offshoot of the disease, affects those as young as 30.
The Study
Alzheimer's is a complex disease, and so too are the attempts to explain it. One way to understand how the brain works to cause the disorder is by using computational modeling, (a series of equations) to characterize an individual aspect that is important to the disease. Biomedical engineers Lydia S. Glaw and Thomas C. Skalak, Ph.D., of the Department of Biomedical Engineering, University of Virginia, Charlottesville, have created a model to examine the role of certain proteins in the development of the disease. Their findings are contained in the study entitled A Computational Model of the Role of Presenilin-1 and Glycogen Synthase Kinase-3 in Familial Alzheimer's Disease. They will present their findings at the 122nd Annual Meeting of the American Physiological Society, which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.
The researchers constructed a simple computational model to measure plaques and tangles and their influence in causing FAD. The model tested the hypothesis that certain variables - genetic mutations in proteins and "tau" tangles - might be predicative of the development of the disease. The main hypothesis that the model tested was the idea that GSK3 is a link between amyloid beta buildup and tau tangle development.
Brain Plaque: A Major Instigator?
The proteins presenilin-1 (PS1) (a mutated gene found in familial AD) and glycogen synthase kinase (GSK-3) (a protein) and amyloid beta (A??) plaque (amino acids that are found in large quantity in AD) were studied to quantitatively examine their roles in the development of Alzheimer's pathology. The elements (in the form of existing research data) were applied to the model, which was constructed of kinetic equations developed from literature searches, and analyzed the interactions of the proteins and complexes under various scenarios. The model is a first-of-its-kind approach to modeling, understanding and predicting Alzheimer's pathways.
Results: No Link Between A Protein and Plaques, Tangles
GSK3 had a large effect on tangle formation, but very little on the plaques. Activating GSK3 was not found to be sufficient to cause changes in the brain to the extent seen in Alzheimer's patients. However, overproduction of GSK3 as opposed to activation may be able to cause those changes. Nor was there any link found between amyloid beta plaque and tau tangles. The main conclusion of the model so far is that no single change to the system can cause Alzheimer's disease. Multiple changes, such as a PS1 mutation combined with GSK3 over-activation can, however. A multi-pronged approach to treating the disease may be best.
Conclusion
Glaw's model can be used for additional pathway analysis. She views modeling as a useful way for better understanding this complex, multi-layered disease.
Source:
Donna Krupa
American Physiological Society
The Study
Alzheimer's is a complex disease, and so too are the attempts to explain it. One way to understand how the brain works to cause the disorder is by using computational modeling, (a series of equations) to characterize an individual aspect that is important to the disease. Biomedical engineers Lydia S. Glaw and Thomas C. Skalak, Ph.D., of the Department of Biomedical Engineering, University of Virginia, Charlottesville, have created a model to examine the role of certain proteins in the development of the disease. Their findings are contained in the study entitled A Computational Model of the Role of Presenilin-1 and Glycogen Synthase Kinase-3 in Familial Alzheimer's Disease. They will present their findings at the 122nd Annual Meeting of the American Physiological Society, which is part of the Experimental Biology 2009 scientific conference. The meeting will be held April 18-22, 2009 in New Orleans.
The researchers constructed a simple computational model to measure plaques and tangles and their influence in causing FAD. The model tested the hypothesis that certain variables - genetic mutations in proteins and "tau" tangles - might be predicative of the development of the disease. The main hypothesis that the model tested was the idea that GSK3 is a link between amyloid beta buildup and tau tangle development.
Brain Plaque: A Major Instigator?
The proteins presenilin-1 (PS1) (a mutated gene found in familial AD) and glycogen synthase kinase (GSK-3) (a protein) and amyloid beta (A??) plaque (amino acids that are found in large quantity in AD) were studied to quantitatively examine their roles in the development of Alzheimer's pathology. The elements (in the form of existing research data) were applied to the model, which was constructed of kinetic equations developed from literature searches, and analyzed the interactions of the proteins and complexes under various scenarios. The model is a first-of-its-kind approach to modeling, understanding and predicting Alzheimer's pathways.
Results: No Link Between A Protein and Plaques, Tangles
GSK3 had a large effect on tangle formation, but very little on the plaques. Activating GSK3 was not found to be sufficient to cause changes in the brain to the extent seen in Alzheimer's patients. However, overproduction of GSK3 as opposed to activation may be able to cause those changes. Nor was there any link found between amyloid beta plaque and tau tangles. The main conclusion of the model so far is that no single change to the system can cause Alzheimer's disease. Multiple changes, such as a PS1 mutation combined with GSK3 over-activation can, however. A multi-pronged approach to treating the disease may be best.
Conclusion
Glaw's model can be used for additional pathway analysis. She views modeling as a useful way for better understanding this complex, multi-layered disease.
Source:
Donna Krupa
American Physiological Society
четверг, 7 июля 2011 г.
Study Implicates Defective Synapse Generator In Onset Of Alzheimer's - Finding Links Age-related Brain Disease To Down Syndrome
A new UCLA/Veterans Affairs study implicates defects in the machinery that creates connections between brain cells as responsible for the onset of Alzheimer disease.
The defect in PAK enzyme signaling pathways -- vital to creation of these connections, or synapses -- is related to loss of a synapse protein in certain forms of mental retardation, such as Down syndrome. The new finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.
The peer-reviewed journal Nature Neuroscience published the study online Jan. 15.
"The emerging lesson is that cognitive problems in Alzheimer disease are related to defects in the machinery controlling neuronal connections, not the lesions observed by pathologists," said principal investigator Greg Cole, professor of medicine and neurology at the David Geffen School of Medicine and Alzheimer Disease Research Center at UCLA, and the Geriatric Research Education and Clinical Center at the Veterans Affairs Greater Los Angeles Health Care System and Sepulveda Ambulatory Care Center. "Our findings show that PAK defects in the brains of Alzheimer patients appear sufficient to directly cause cognitive difficulties."
In some families, early-onset Alzheimer disease can be caused by mutations in different genes that all increase the production of a sticky protein called Abeta42 (Ab42). The increase causes the protein to form aggregates, little clusters or long filaments that pile up and make lesions in the brain called plaques.
Ab42 is widely believed to cause Alzheimer, but the process remains unclear. Soluble Ab42 aggregates called "oligomers" are now considered as a major toxic form of Ab42 and therefore implicated in loss of synapses and memory.
This new study implicates the PAK enzyme-signaling pathway, which is known to play a role in synapse formation and developmental cognitive deficits, or mental retardation.
The PAK enzymes form a family that includes two members known to localize to synapses (PAK1 and PAK3). Both are known to play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. Both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients to an extent sufficient to contribute to cognitive decline.
The research team finds that blocking these PAKs in middle-aged mice causes memory loss together with deficits in a protein involved in making neuronal connections. In humans, the same protein shows large losses in Alzheimer as well as in Down syndrome, the most common cause of mental retardation.
The study also shows in cultures and animal models that Ab42 oligomers induce defects in PAK similar to those seen in Alzheimer disease, and selective loss of the same neuronal connection protein lost in Alzheimer disease and Down syndrome. The findings suggest PAK loss in Alzheimer brains is sufficient to directly cause these cognitive deficits.
Sally Frautschy, associate professor of medicine at the UCLA Geffen School of Medicine and a researcher at the VA's Geriatric Research Education and Clinical Center, is a co investigator. In addition to UCLA and the VA, the research team included neuroscientists affiliated with Laval University Medical Center in Quebec, Canada, and Osaka University in Japan.
Funding for the study was provided by the VA, the National Institutes of Health, the UCLA Alzheimer Disease Research Center, the UCLA Claude Pepper Older Americans Independence Center and the National Institute of Aging.
Copy of full study online.
The Alzheimer Disease Research Center at UCLA, directed by Dr. Jeffrey L. Cummings, was established in 1991 with a grant from the National Institute on Aging. Together with grants from the Alzheimer's Disease Research Center of California and the Sidell-Kagan Foundation, the center provides a mechanism for integrating, coordinating and supporting new and ongoing research by established investigators in Alzheimer disease and aging. Information about clinical care and research at the center is available by telephone at (310) 206-3779 or online at adc.ucla
The Department of Neurology at UCLA's David Geffen School of Medicine encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks No. 2 among its peers nationwide in National Institutes of Health funding.
Veterans Affairs Greater Los Angeles Health Care System and Sepulveda Ambulatory Care Center combine resources to form a unified Geriatric Research Education and Clinical Center, one of 20 nationwide. These centers of excellence are designed to improve health care and quality of life to older veterans through the advancement and integration of research, education and clinical achievements in geriatrics and gerontology into the total VA health care system and broader communities.
Additional online resources:
-- David Geffen School of Medicine at UCLA:
medsch.ucla.
-- UCLA Alzheimer Disease Research Center:
adc.ucla.
-- VA Geriatric Research, Education and Clinical Center:
grecc-gla/mission.htm.
Dan Page
dpagemednet.ucla
University of California - Los Angeles
newsroom.ucla
The defect in PAK enzyme signaling pathways -- vital to creation of these connections, or synapses -- is related to loss of a synapse protein in certain forms of mental retardation, such as Down syndrome. The new finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.
The peer-reviewed journal Nature Neuroscience published the study online Jan. 15.
"The emerging lesson is that cognitive problems in Alzheimer disease are related to defects in the machinery controlling neuronal connections, not the lesions observed by pathologists," said principal investigator Greg Cole, professor of medicine and neurology at the David Geffen School of Medicine and Alzheimer Disease Research Center at UCLA, and the Geriatric Research Education and Clinical Center at the Veterans Affairs Greater Los Angeles Health Care System and Sepulveda Ambulatory Care Center. "Our findings show that PAK defects in the brains of Alzheimer patients appear sufficient to directly cause cognitive difficulties."
In some families, early-onset Alzheimer disease can be caused by mutations in different genes that all increase the production of a sticky protein called Abeta42 (Ab42). The increase causes the protein to form aggregates, little clusters or long filaments that pile up and make lesions in the brain called plaques.
Ab42 is widely believed to cause Alzheimer, but the process remains unclear. Soluble Ab42 aggregates called "oligomers" are now considered as a major toxic form of Ab42 and therefore implicated in loss of synapses and memory.
This new study implicates the PAK enzyme-signaling pathway, which is known to play a role in synapse formation and developmental cognitive deficits, or mental retardation.
The PAK enzymes form a family that includes two members known to localize to synapses (PAK1 and PAK3). Both are known to play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. Both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients to an extent sufficient to contribute to cognitive decline.
The research team finds that blocking these PAKs in middle-aged mice causes memory loss together with deficits in a protein involved in making neuronal connections. In humans, the same protein shows large losses in Alzheimer as well as in Down syndrome, the most common cause of mental retardation.
The study also shows in cultures and animal models that Ab42 oligomers induce defects in PAK similar to those seen in Alzheimer disease, and selective loss of the same neuronal connection protein lost in Alzheimer disease and Down syndrome. The findings suggest PAK loss in Alzheimer brains is sufficient to directly cause these cognitive deficits.
Sally Frautschy, associate professor of medicine at the UCLA Geffen School of Medicine and a researcher at the VA's Geriatric Research Education and Clinical Center, is a co investigator. In addition to UCLA and the VA, the research team included neuroscientists affiliated with Laval University Medical Center in Quebec, Canada, and Osaka University in Japan.
Funding for the study was provided by the VA, the National Institutes of Health, the UCLA Alzheimer Disease Research Center, the UCLA Claude Pepper Older Americans Independence Center and the National Institute of Aging.
Copy of full study online.
The Alzheimer Disease Research Center at UCLA, directed by Dr. Jeffrey L. Cummings, was established in 1991 with a grant from the National Institute on Aging. Together with grants from the Alzheimer's Disease Research Center of California and the Sidell-Kagan Foundation, the center provides a mechanism for integrating, coordinating and supporting new and ongoing research by established investigators in Alzheimer disease and aging. Information about clinical care and research at the center is available by telephone at (310) 206-3779 or online at adc.ucla
The Department of Neurology at UCLA's David Geffen School of Medicine encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation, and neurovascular disorders. The department ranks No. 2 among its peers nationwide in National Institutes of Health funding.
Veterans Affairs Greater Los Angeles Health Care System and Sepulveda Ambulatory Care Center combine resources to form a unified Geriatric Research Education and Clinical Center, one of 20 nationwide. These centers of excellence are designed to improve health care and quality of life to older veterans through the advancement and integration of research, education and clinical achievements in geriatrics and gerontology into the total VA health care system and broader communities.
Additional online resources:
-- David Geffen School of Medicine at UCLA:
medsch.ucla.
-- UCLA Alzheimer Disease Research Center:
adc.ucla.
-- VA Geriatric Research, Education and Clinical Center:
grecc-gla/mission.htm.
Dan Page
dpagemednet.ucla
University of California - Los Angeles
newsroom.ucla
понедельник, 4 июля 2011 г.
The Existence Of Alzheimer's As A 'Disease' Challenged By International Brain Aging Expert
Case Western Reserve University School of Medicine professor of neurology, Peter Whitehouse, M.D., Ph.D., challenges conventional wisdom and assumptions of brain aging in his new book, "The Myth of Alzheimer's: What You Aren't Being Told About Today's Most Dreaded Disease." In his provocative and ground-breaking new book, Dr. Whitehouse questions current approaches to Alzheimer's disease (AD) diagnosis and treatment and brings a new understanding to everything we thought we knew about brain aging. Dr. Whitehouse and co-author Daniel George, M. Sc., published "The Myth of Alzheimer's" to expose what they believe to be the unsound clinical, political, and scientific framework of AD and explain why it continues to be so difficult to address a condition concerning so many people as they age.
According to the founder of the University Memory and Aging Center at Case Western Reserve University and University Hospitals Case Medical Center, "AD cannot be biologically or clinically differentiated from normal aging. There is no one profile of AD that is consistent from person to person," says Dr. Whitehouse. "Alzheimer's is a heterogeneous process because it reflects the different way people's brains age over their lifetimes." The book claims AD represents our culture's attempt to make sense of a natural process of brain aging that we cannot control; all the biological hallmarks of AD are also the hallmarks of normal, albeit severe, forms of brain aging. "The promise of a panacea for one of our most dreaded 'diseases' is a powerful cultural myth," says Whitehouse, "and one purveyed by powerful pharmaceutical companies, advocacy organizations, and private researchers with much profit to gain." The book points out that most scientists in the field of AD research believe a cure is unlikely and we need to invest our dollars more wisely by putting them toward prevention and care rather than predominantly in a cure.
Based on twenty-five years as a clinician and educator caring for persons with aging associated cognitive challenges and on his experience as the co-founder (with his wife Catherine) of an internationally recognized and nationally awarding wining intergenerational school affiliated with Case Western Reserve, Dr. Whitehouse shares his experiences and accumulated wisdom about ageing well.
The term "Alzheimer's disease" generates fear, paranoia, angst, and stigmatization while evoking powerful social and emotional images. For the millions of people diagnosed with AD and their families, this book will help them understand why what they have been told may be incomplete, even wrong; why the treatment they are probably being given is inadequate; and most importantly, how they can get the help they need. "The Myth of Alzheimer's" encourages readers to think about brain aging not as a disease, but as a lifelong process fraught with challenges which will change society's whole approach to aging and add quality to our later years and to the lives of those we love.
With a caring, yet scientifically grounded, message of prevention, Whitehouse and George explore measures to enhance the likelihood of successful cognitive aging, and presents examples of how to maintain cognitive vitality and a sense of fulfillment and social contribution as we age. Deemed a "landmark book" by Harry Moody of the AARP, "The Myth of Alzheimer's" provides answers for when to see a doctor for memory loss, how to find the right medical team, and how to develop a collaborative relationship with your physician.
Backed up by extensive research, full of practical advice and information, and infused with hope, Dr. Whitehouse and Mr. George's book strives to liberate people from the crippling label of AD and teach them how to best approach memory loss and learn how to age with wisdom, while preserving their quality of life.
"The Myth of Alzheimer's" answers important questions such as:
* Is Alzheimer's actually a disease?
* What is the difference between a naturally aging brain and an Alzheimer's brain?
* How effective are the current drugs for AD? Are they worth the money we spend on them?
* What kind of hope does science really have for the treatment of memory loss? Are there alternative interventions that can keep our aging bodies and minds sharp?
* What promise does genetic research actually hold?
* What would a world without Alzheimer's look like and how do we as individuals and as human communities get there?
For more information on "The Myth of Alzheimer's" visit themythofalzheimers/.
About the Authors
Peter Whitehouse, M.D., Ph.D., one of the best known Alzheimer's experts in the world, specializes in neurology with an interest in geriatrics and cognitive science. He is the founder of the University Alzheimer Center (now the University Memory and Aging Center) at Case Western Reserve University and University Hospitals Case Medical Center. His most recent work includes ethics, integrative health care, and quality of life.
Danny George, M.Sc. works at the Memory and Aging Center in Cleveland, Ohio, and is currently pursuing a Ph.D. in Medical Anthropology at Oxford University in England.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and 12th largest among the nation's medical schools for research funding from the National Institutes of Health. Eleven Nobel Laureates have been affiliated with the school. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching and in 2002, became the third medical school in history to receive a pre-eminent review from the national body responsible for accrediting the nation's academic medical institutions. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century.
Annually, the School of Medicine trains more than 600 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report Guide to Graduate Education.
The School of Medicine's primary clinical affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic Foundation, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. casemed.case/.
Source: Jessica Studeny
Case Western Reserve University
According to the founder of the University Memory and Aging Center at Case Western Reserve University and University Hospitals Case Medical Center, "AD cannot be biologically or clinically differentiated from normal aging. There is no one profile of AD that is consistent from person to person," says Dr. Whitehouse. "Alzheimer's is a heterogeneous process because it reflects the different way people's brains age over their lifetimes." The book claims AD represents our culture's attempt to make sense of a natural process of brain aging that we cannot control; all the biological hallmarks of AD are also the hallmarks of normal, albeit severe, forms of brain aging. "The promise of a panacea for one of our most dreaded 'diseases' is a powerful cultural myth," says Whitehouse, "and one purveyed by powerful pharmaceutical companies, advocacy organizations, and private researchers with much profit to gain." The book points out that most scientists in the field of AD research believe a cure is unlikely and we need to invest our dollars more wisely by putting them toward prevention and care rather than predominantly in a cure.
Based on twenty-five years as a clinician and educator caring for persons with aging associated cognitive challenges and on his experience as the co-founder (with his wife Catherine) of an internationally recognized and nationally awarding wining intergenerational school affiliated with Case Western Reserve, Dr. Whitehouse shares his experiences and accumulated wisdom about ageing well.
The term "Alzheimer's disease" generates fear, paranoia, angst, and stigmatization while evoking powerful social and emotional images. For the millions of people diagnosed with AD and their families, this book will help them understand why what they have been told may be incomplete, even wrong; why the treatment they are probably being given is inadequate; and most importantly, how they can get the help they need. "The Myth of Alzheimer's" encourages readers to think about brain aging not as a disease, but as a lifelong process fraught with challenges which will change society's whole approach to aging and add quality to our later years and to the lives of those we love.
With a caring, yet scientifically grounded, message of prevention, Whitehouse and George explore measures to enhance the likelihood of successful cognitive aging, and presents examples of how to maintain cognitive vitality and a sense of fulfillment and social contribution as we age. Deemed a "landmark book" by Harry Moody of the AARP, "The Myth of Alzheimer's" provides answers for when to see a doctor for memory loss, how to find the right medical team, and how to develop a collaborative relationship with your physician.
Backed up by extensive research, full of practical advice and information, and infused with hope, Dr. Whitehouse and Mr. George's book strives to liberate people from the crippling label of AD and teach them how to best approach memory loss and learn how to age with wisdom, while preserving their quality of life.
"The Myth of Alzheimer's" answers important questions such as:
* Is Alzheimer's actually a disease?
* What is the difference between a naturally aging brain and an Alzheimer's brain?
* How effective are the current drugs for AD? Are they worth the money we spend on them?
* What kind of hope does science really have for the treatment of memory loss? Are there alternative interventions that can keep our aging bodies and minds sharp?
* What promise does genetic research actually hold?
* What would a world without Alzheimer's look like and how do we as individuals and as human communities get there?
For more information on "The Myth of Alzheimer's" visit themythofalzheimers/.
About the Authors
Peter Whitehouse, M.D., Ph.D., one of the best known Alzheimer's experts in the world, specializes in neurology with an interest in geriatrics and cognitive science. He is the founder of the University Alzheimer Center (now the University Memory and Aging Center) at Case Western Reserve University and University Hospitals Case Medical Center. His most recent work includes ethics, integrative health care, and quality of life.
Danny George, M.Sc. works at the Memory and Aging Center in Cleveland, Ohio, and is currently pursuing a Ph.D. in Medical Anthropology at Oxford University in England.
About Case Western Reserve University School of Medicine
Founded in 1843, Case Western Reserve University School of Medicine is the largest medical research institution in Ohio and 12th largest among the nation's medical schools for research funding from the National Institutes of Health. Eleven Nobel Laureates have been affiliated with the school. The School of Medicine is recognized throughout the international medical community for outstanding achievements in teaching and in 2002, became the third medical school in history to receive a pre-eminent review from the national body responsible for accrediting the nation's academic medical institutions. The School's innovative and pioneering Western Reserve2 curriculum interweaves four themes--research and scholarship, clinical mastery, leadership, and civic professionalism--to prepare students for the practice of evidence-based medicine in the rapidly changing health care environment of the 21st century.
Annually, the School of Medicine trains more than 600 M.D. and M.D./Ph.D. students and ranks in the top 25 among U.S. research-oriented medical schools as designated by U.S. News and World Report Guide to Graduate Education.
The School of Medicine's primary clinical affiliate is University Hospitals Case Medical Center and is additionally affiliated with MetroHealth Medical Center, the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, and the Cleveland Clinic Foundation, with which it established the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in 2002. casemed.case/.
Source: Jessica Studeny
Case Western Reserve University
пятница, 1 июля 2011 г.
Medivation Plans To Initiate Pivotal Confirmatory Phase 3 Trial Of Dimebon(TM) For Alzheimer's Disease In Second Quarter Of 2008
Medivation, Inc.
(Nasdaq: MDVN) announced that, based on its end-of-Phase 2 meeting
with the U.S. Food and Drug Administration (FDA), the Company plans to
begin a pivotal confirmatory Phase 3 trial of Dimebon(TM) for
mild-to-moderate Alzheimer's Disease in the second quarter of 2008.
The FDA informed Medivation that the company's previously completed
trial conducted in Russia can be used as one of the two pivotal studies
required to support the approval of Dimebon to treat mild-to-moderate
Alzheimer's disease, as long as a significant proportion of the sites in
the confirmatory Phase 3 trial are located in the United States.
"We are now a Phase 3 company with clear regulatory guidance on the
pivotal trials required to seek marketing approval for Dimebon in the
United States," said David T. Hung, M.D., president and chief executive
officer of Medivation. "This is a significant step forward for Medivation,
and validates our strategy to advance Dimebon directly into a pivotal Phase
3 trial."
The Phase 3 clinical trial will enroll approximately 525 patients with
mild-to-moderate Alzheimer's disease at sites in the United States, Europe
and South America. Patients will be randomized to one of three treatment
groups: Dimebon 20 mg three times per day (TID); Dimebon 5 mg TID; and
placebo. Patients will be treated for six months and may not be taking any
other Alzheimer's disease drugs. The primary endpoints are the Alzheimer's
Disease Assessment Scale - cognitive subscale (ADAS-cog) and the
Clinician's Interview-Based Impression of Change plus caregiver interview
(CIBIC-plus).
In the previously completed trial Dimebon-treated patients were
significantly improved over placebo patients on both the ADAS-cog and
CIBIC-plus, with p values of less than 0.0001. This level of statistical
significance is several times better than what is required to obtain
marketing approval.
"We changed as little as possible in the design of the Phase 3 trial
given the highly statistically significant results of our previous trial,"
said Lynn Seely, M.D., chief medical officer of Medivation. "The primary
endpoints, duration of treatment and patient inclusion and exclusion
criteria are all substantially identical to the previous trial. The primary
differences are that the Phase 3 trial will be global and will test two
doses of Dimebon -- the dose studied in the previous trial plus a lower
dose to address the regulatory recommendation that minimum effective dose
be explored in the development of investigational drugs."
Medivation expects to complete the pivotal confirmatory Phase 3 trial
and apply for marketing approval in 2010.
About Medivation
Medivation, Inc. is a biopharmaceutical company with small molecule
drugs in clinical development to treat three large, unmet medical needs --
Alzheimer's disease, Huntington's disease and hormone-refractory prostate
cancer. For more information, please go to medivation.
This press release contains forward-looking statements, which are made
pursuant to the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements involve risks and
uncertainties that could cause actual results to differ significantly from
those projected. You are cautioned not to place undue reliance on the
forward-looking statements, which speak only as of the date of this
release. None of the Company's product candidates has been approved for
sale, significant additional animal and human testing is required in order
to seek marketing approval for any of its product candidates, and
Medivation cannot assure you that marketing approval can be obtained for
any of its product candidates. Furthermore, as is typically the case at
this stage of the regulatory review process, the FDA has not yet performed
an in-depth review of Medivation's preclinical and clinical data, so its
views remain subject to change. Medivation's filings with the Securities
and Exchange Commission, including its Annual Report on Form 10-KSB for the
year ended December 31, 2006, include information about additional factors
that could affect the Company's financial and operating results.
Medivation, Inc
medivation
(Nasdaq: MDVN) announced that, based on its end-of-Phase 2 meeting
with the U.S. Food and Drug Administration (FDA), the Company plans to
begin a pivotal confirmatory Phase 3 trial of Dimebon(TM) for
mild-to-moderate Alzheimer's Disease in the second quarter of 2008.
The FDA informed Medivation that the company's previously completed
trial conducted in Russia can be used as one of the two pivotal studies
required to support the approval of Dimebon to treat mild-to-moderate
Alzheimer's disease, as long as a significant proportion of the sites in
the confirmatory Phase 3 trial are located in the United States.
"We are now a Phase 3 company with clear regulatory guidance on the
pivotal trials required to seek marketing approval for Dimebon in the
United States," said David T. Hung, M.D., president and chief executive
officer of Medivation. "This is a significant step forward for Medivation,
and validates our strategy to advance Dimebon directly into a pivotal Phase
3 trial."
The Phase 3 clinical trial will enroll approximately 525 patients with
mild-to-moderate Alzheimer's disease at sites in the United States, Europe
and South America. Patients will be randomized to one of three treatment
groups: Dimebon 20 mg three times per day (TID); Dimebon 5 mg TID; and
placebo. Patients will be treated for six months and may not be taking any
other Alzheimer's disease drugs. The primary endpoints are the Alzheimer's
Disease Assessment Scale - cognitive subscale (ADAS-cog) and the
Clinician's Interview-Based Impression of Change plus caregiver interview
(CIBIC-plus).
In the previously completed trial Dimebon-treated patients were
significantly improved over placebo patients on both the ADAS-cog and
CIBIC-plus, with p values of less than 0.0001. This level of statistical
significance is several times better than what is required to obtain
marketing approval.
"We changed as little as possible in the design of the Phase 3 trial
given the highly statistically significant results of our previous trial,"
said Lynn Seely, M.D., chief medical officer of Medivation. "The primary
endpoints, duration of treatment and patient inclusion and exclusion
criteria are all substantially identical to the previous trial. The primary
differences are that the Phase 3 trial will be global and will test two
doses of Dimebon -- the dose studied in the previous trial plus a lower
dose to address the regulatory recommendation that minimum effective dose
be explored in the development of investigational drugs."
Medivation expects to complete the pivotal confirmatory Phase 3 trial
and apply for marketing approval in 2010.
About Medivation
Medivation, Inc. is a biopharmaceutical company with small molecule
drugs in clinical development to treat three large, unmet medical needs --
Alzheimer's disease, Huntington's disease and hormone-refractory prostate
cancer. For more information, please go to medivation.
This press release contains forward-looking statements, which are made
pursuant to the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995. Forward-looking statements involve risks and
uncertainties that could cause actual results to differ significantly from
those projected. You are cautioned not to place undue reliance on the
forward-looking statements, which speak only as of the date of this
release. None of the Company's product candidates has been approved for
sale, significant additional animal and human testing is required in order
to seek marketing approval for any of its product candidates, and
Medivation cannot assure you that marketing approval can be obtained for
any of its product candidates. Furthermore, as is typically the case at
this stage of the regulatory review process, the FDA has not yet performed
an in-depth review of Medivation's preclinical and clinical data, so its
views remain subject to change. Medivation's filings with the Securities
and Exchange Commission, including its Annual Report on Form 10-KSB for the
year ended December 31, 2006, include information about additional factors
that could affect the Company's financial and operating results.
Medivation, Inc
medivation
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