Science Current Events | Science News | Brightsurf.com
 

Rejected Alzheimer's drug shows new potential

July 31, 2012
Study suggests that latrepirdine, which previously failed in clinical trials, may be successful if tested on patients with earlier stages of the disease

An international team of scientists led by researchers at Mount Sinai School Medicine have discovered that a drug that had previously yielded conflicting results in clinical trials for Alzheimer's disease effectively stopped the progression of memory deterioration and brain pathology in mouse models of early stage Alzheimer's disease. The findings, published July 31, 2012 in Molecular Psychiatry, demonstrate renewed potential for this compound and could lead to clinical trials in patients with early stages of the disease.

Latrepirdine, known commercially as Dimebon, was initially sold as an antihistamine in Russia, approved for use there in 1983. In the 1990s, researchers at the Institute of Physiologically Active Compounds in Moscow determined that the compound appeared effective in treating Alzheimer's disease in animals. They continued their research in humans and performed several studies, including Phase I and II trials, all of which showed significant and sustained improvement in cognitive behavior with minimal side effects. The Phase II trials, performed in Russia, were overseen by U.S. Alzheimer's researchers, including Mary Sano, PhD, Director of the Mount Sinai Alzheimer's Disease Research Center.

However, when research was continued in the United States in a Phase III trial, the drug did not demonstrate any improvement in people with the disease, causing the sponsors to halt further clinical study of the drug in Alzheimer's disease. Some researchers have speculated that the Russian patients might have had different disease stage or subtype of Alzheimer's, and therefore were more responsive to treatment than the patients in the Phase III trials in the United States.

Before the failed trials were announced, researchers at Mount Sinai School of Medicine, led by Sam Gandy, MD, PhD, Professor of Neurology, and Psychiatry, and Director of the Mount Sinai Center for Cognitive Health, began studying the mechanism of action behind latrepirdine in the current study, which is supported by the Cure Alzheimer's Fund.

Dr. Gandy's team randomly administered either latrepirdine or placebo to mice engineered to present the early stages of Alzheimer's disease and found that the drug halted both behavioral decline and progression of neuropathology. In evaluating how latrepirdine improved memory, John Steele, PhD, a neuroscience graduate student working with Dr. Gandy, and Lenard Lachenmayer, MD, a postdoctoral fellow working under the supervision of Zhenyu Yue, PhD, Associate Professor of Neurology at Mount Sinai, found that the drug enhanced autophagy, the so-called "self-eating" process of cells that protects the brain from neurodegeneration.

"When we learned that latrepirdine failed in patients in the United States in 2010, scientists around the world were disappointed and perplexed," Dr. Gandy said. "We wanted to find out why the drug did so well in Russia but then showed no effect in the global studies. The findings from our animal model studies indicated that this drug should not be discarded, and that, if its mechanism of action can be optimized, it still has potential."

Dr. Sano points out that not only did latrepirdene have significant and sustained effect in the Russian study but it also showed a mild effect in one study of patients with Huntington's disease.

"Since cognitive benefit is what really matters to patients and families, it is critical that we explore every mechanism by which it might occur," Dr. Sano said.

"While this is just the beginning, our research shows that this previously cast-off drug still has strong therapeutic promise," Dr. Gandy said. "Autophagy drugs are believed to hold great promise for a range of neurodegenerative diseases, and these data raise the question of whether further basic science work on latrepirdine might lead to optimization of the drug so that a more potent drug could be developed, and subsequently tested in human clinical trials.

"This is especially true since we know that latrepirdine is an extremely safe drug and in view of the recent failure of the first key trial of the drug bapineuzumab," Dr. Gandy added. "Also, as may be the case with all amyloid-lowering drugs, initiating latrepirdine trials before amyloid deposition begins may be the key. Now, with the new brain amyloid scans that began at Mount Sinai in June, we can easily establish who those patients are."

Looking ahead, Drs. Gandy, Yue, and their collaborators are planning to test latrepirdine in mouse models of other protein buildup diseases such as Parkinson's disease, Lewy body dementia, and chronic traumatic encephalopathy, the Alzheimer's-like condition athletes endure from boxing, football and hockey. Dr. Sano notes that so few agents show any improvement in cognition that it is critical that to exhaust every potential lead.

Mount Sinai has a long-standing legacy of critical breakthroughs in team research in Alzheimer's disease. Dr. Gandy is an internationally-renowned expert in understanding the amyloid plaques characteristic of Alzheimer's disease, and he led a team of researchers to the discovery of the first drugs that reduced amyloid buildup. Dr. Sano is a world leader in designing clinical trials to find treatments and preventions for cognitive loss and Alzheimer's disease. Together, their labs and the Mount Sinai Alzheimer's Disease Research Center and Center for Cognitive Health are focused on a strategic approach to translating clinical challenges into bench investigations and back.

The Mount Sinai Hospital / Mount Sinai School of Medicine


Related Alzheimer's Disease Current Events and Alzheimer's Disease News Articles


Gout may lessen chances of developing Alzheimer's disease
Gout appears to have a protective effect for the brain, possibly thanks to uric acid, the chemical in a person's blood that can crystallize, leading to gout, said a team of researchers from north America.

Study reveals mechanism behind most common form of inherited Alzheimer's disease
A study from researchers at Massachusetts General Hospital (MGH) and Brigham and Women's Hospital (BWH) reveals for the first time exactly how mutations associated with the most common form of inherited Alzheimer's disease produce the disorder's devastating effects.

LSU Health New Orleans discovers retina protein that may help conquer blindness
Research led by Nicolas Bazan, MD, PhD, Boyd Professor and Director of the LSU Health New Orleans Neuroscience Center of Excellence, discovered a protein in the retina that is crucial for vision.

Neuropsychological, neuropsychiatric and functional tests help follow the course of Alzheimer's
The cognitive performance of persons with Alzheimer's disease and behavioural and psychological problems are linked to their performance of activities of daily living, according to a recent study completed at the University of Eastern Finland.

Time to 'just say no' to behavior-calming drugs for Alzheimer patients? Experts say yes
Doctors write millions of prescriptions a year for drugs to calm the behavior of people with Alzheimer's disease and other types of dementia.

Vanderbilt study shows poor heart function could be major risk for Alzheimer's disease
A healthier heart could prevent Alzheimer's disease, according to new research at Vanderbilt University Medical Center.

UCLA researchers devise new method to identify disease markers
UCLA life scientists have created an accurate new method to identify genetic markers for many diseases -- a significant step toward a new era of personalized medicine, tailored to each person's DNA and RNA.

Neuron groups, not single cells, maintain brain stability
To compensate for erratic shifts and spikes in its neuronal communications, the brain relies on the stabilizing mechanism called "homeostasis" -- the ability to maintain relatively stable equilibrium between different elements of its composition -- to preserve overall network function. Disruptions in stability cause disorders such as epilepsy, but precious little is known about this macro-level regulatory phenomenon.

Joslin scientists find direct link between insulin resistance and behavioral disorders
People with diabetes are more prone to anxiety and depression than those with other chronic diseases that require similar levels of management. The reasons for this aren't well understood, but Joslin Diabetes Center researchers have discovered one potential explanation.

Genetic discovery may help determine effectiveness of Huntington's disease treatments
A new genetic discovery in the field of Huntington's disease (HD) could mean a more effective way in determining severity of this neurological disease when using specific treatments.
More Alzheimer's Disease Current Events and Alzheimer's Disease News Articles

Alzheimer's Disease: What If There Was a Cure?

Alzheimer's Disease: What If There Was a Cure?
by Mary T. Newport (Author)


The first edition of Alzheimer's Disease: What if There Was a Cure?, which details Dr. Newport's discovery and use of medium-chain fatty acids (which act like alternative fuel in the Alzheimer's brain), had such a strong reception in 2011 that a second edition is now in demand. In this updated and expanded version, Dr. Newport, a neonatal practitioner, continues the story of her husband Steve's progress and provides the most recent research on the possible connection between Alzheimer's disease and the herpes simplex virus and nitrosamine substances, as well as how infection, inflammation, and genetic makeup may affect an individual's response to fatty acid therapy. Among many other updates, Dr. Newport details the latest clinicaltrials aimed at removing beta-amyloid, which accumulates in...

Caring for a Person with Alzheimer's Disease

Caring for a Person with Alzheimer's Disease
by National Institute on Aging U.S. Department of Health and Human Services (Author)


This comprehensive handbook offers information and advice for at-home caregivers of people with Alzheimer's disease. It addresses all aspects of care, from bathing and eating to visiting the doctor and getting respite care.

Alzheimer's Disease: What If There Was a Cure?

Alzheimer's Disease: What If There Was a Cure?
by Mary T. Newport (Author), Cheryl Hirsch (Editor)


Though Dr. Mary T. Newport has provided professional care to newborns since 1983, she's led a double life since 2000 when she became a caregiver at home. That's when her beloved husband, Steve, first showed signs of Alzheimer's disease. After his deterioration accelerated in 2004, Dr. Newport began avidly researching ways to keep him functional for as long as possible. Since she understands medical terminology and scientific methods, she was thrilled to find new research showing that medium- chain fatty acids, which act like an alternative fuel in the insulin-deficient Alzheimer's brain, can sometimes reverse or at least stabilize the disease. When she gave Steve about 2 tablespoons of coconut oil (a source of these fats) at breakfast before a memory test that he had previously failed,...

Alzheimer's Treatment Alzheimer's Prevention: A Patient and Family Guide, 2012 Edition

Alzheimer's Treatment Alzheimer's Prevention: A Patient and Family Guide, 2012 Edition
by Dr. Richard S Isaacson MD (Author)


Harvard-trained Neurologist Dr. Richard Isaacson answers the most common patient and caregiver questions on the treatment and prevention of Alzheimer's disease (AD). He shares his cutting edge, comprehensive approach in the fight against AD, the greatest public health crisis today. This groundbreaking book has been written especially for patients, caregivers, family members, and allied healthcare professionals. Dr. Isaacson writes in easy to understand terms and easy to read (larger-type) print to help educate and inform those confronting AD. He outlines his comprehensive and scientifically-based approach that includes a comprehenisve 9-week diet and nutrition plan, with examples of what to eat, what not to eat, and a food terminology guide to help read and understand nutrition labels. ...

Developing Support Groups for Individuals with Early-Stage Alzheimer's Disease: Planning, Implementation, and Evaluation

Developing Support Groups for Individuals with Early-Stage Alzheimer's Disease: Planning, Implementation, and Evaluation
by Robyn Yale L.C.S.W. (Author)


This one-of-a-kind, step-by-step guidebook has been used as a national and international model to meet the needs of people diagnosed with Alzheimer's disease. Clinical and administrative issues include: selecting group participants training facilitators managing unique group topics, interactions and dynamics This book is a must-have for anyone developing early-stage Alzheimer's programs.

Alzheimer's Disease: Advances in Genetics, Molecular and Cellular Biology

Alzheimer's Disease: Advances in Genetics, Molecular and Cellular Biology
by Sangram S. Sisodia (Editor), Rudolph E. Tanzi (Editor)


This book examines every major aspect of Alzheimer disease at a time when there has been no scholarly research volume on the subject published in the last 3-5 years. This edition includes expanded coverage of the cellular-level exploration of related dementing disorders, with in-depth presentation of prion diseases, Pick's disease, fronto-temporal disorders, transgenic models, and biochemistry of presenilins.

The Alzheimer's Solution: How Today's Care Is Failing Millions- and How We Can Do Better

The Alzheimer's Solution: How Today's Care Is Failing Millions- and How We Can Do Better
by Kenneth S. Kosik MD (Author), Ellen Clegg (Author)


As the Baby Boomer generation moves into the ranks of the elderly in the next decade or two, the number of Alzheimer cases expected to develop will be staggering. Since current medical care cannot offer a cure, and even significantly effective treatment is at least ten years away, there is a pressing need for novel solutions to address the multifaceted issues raised by this devastating disease.This book offers a measure of hope and coping strategies for people facing Alzheimer's now or in the future. Authors Kenneth S. Kosik, MD, a neurologist and a leading Alzheimer's researcher, and experienced healthcare journalist Ellen Clegg propose the creation of community centers devoted to Alzheimer's. Here patients and their families could access programs of care, treatment, and most...

Second Forgetting: Remembering the Power of the Gospel during Alzheimer's Disease

Second Forgetting: Remembering the Power of the Gospel during Alzheimer's Disease
by Dr. Benjamin T. Mast (Author), Scotty Smith (Foreword)


Charles is 78 years old and there is much he cannot remember. He cannot remember the names of his children, why he lives in a nursing home, or even whether he ate breakfast today. His forgetting causes confusion, and in his fear and uncertainty he sometimes lashes out at those who try to care for him. But when someone reads a favorite Psalm he quickly joins in, reciting each cherished word. When he hears an old hymn of faith, his hand slowly raises and he breathes out each word quietly, his face reflecting a peace that passes all understanding. Alzheimer’s disease has been described as the “defining disease” of the baby boomer generation. Millions of Americans will spend much of their retirement years either caring for a loved one with Alzheimer’s disease or experiencing its...

The Alzheimer's Diet: A Step-by-Step Nutritional Approach for Memory Loss Prevention and Treatment (Volume 1)

The Alzheimer's Diet: A Step-by-Step Nutritional Approach for Memory Loss Prevention and Treatment (Volume 1)
by Richard S Isaacson MD (Author), Christopher N Ochner PhD (Author)


Harvard-trained Neurologist, Dr. Richard Isaacson and renowned nutrition expert, Dr. Christopher Ochner team up to create this ground-breaking nutritional guide for individuals concerned about memory loss. In recent years, there has been an explosion in research on nutritional interventions for Alzheimer’s prevention and treatment, which is considered to be the most severe public health crisis of our day. These specific dietary interventions present new hope for individuals concerned about memory loss, and also have rapidly expanding scientific-evidence to support their effectiveness. Based on empirical evidence, The Alzheimer’s Diet outlines what to eat, what not to eat, and highlights a step-by-step approach for improving memory and protecting the brain through diet. This...

Alzheimer's Disease: Alzheimer's Stage By Stage, The Alzheimer's Diet And Alzheimer's Caregivers Guide (Alzheimer's Disease, Dementia Help Book 1)

Alzheimer's Disease: Alzheimer's Stage By Stage, The Alzheimer's Diet And Alzheimer's Caregivers Guide (Alzheimer's Disease, Dementia Help Book 1)


Get The Information You NEED To Deal With Alzheimer’s Disease Right Away!
Today only, get this Kindle book for just $2.99. Regularly priced at $5.99. Read on your PC, Mac, smart phone, tablet or Kindle device.

Have you or a loved one been diagnosed with Alzheimer's disease? Are you unsure of what to expect? Things may seem okay today, but Alzheimer's disease eventually will rob you or your loved one of all of the cherished memories and recognition capabilities. How do you know if you are suffering from Alzheimer's disease?

Age-related memory problems and the beginning stages of Alzheimer's disease can look remarkably the same. Download this book NOW and:
Learn What The Signs And Symptoms Of Alzheimer's Disease Are. Learn The Difference Between...

© 2015 BrightSurf.com