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


Americans rate losing eyesight as having greatest impact on their lives
Many Americans across racial and ethnic groups describe losing eyesight as potentially having the greatest impact on their day-to-day life, more so than other conditions including: loss of limb, memory, hearing and speech (57% of African-Americans, 49% of non-Hispanic whites, 43% of Asians and 38% of Hispanics).

Down syndrome helps researchers understand Alzheimer's disease
The link between a protein typically associated with Alzheimer's disease and its impact on memory and cognition may not be as clear as once thought, according to a new study from the University of Wisconsin-Madison's Waisman Center.

Protein variant may boost cardiovascular risk by hindering blood vessel repair
Researchers at UT Southwestern Medical Center have found that the most common variant of the circulating protein apolipoprotein E, called apoE3, helps repair the lining of blood vessels.

Neuroimaging technique identifies concussion-related brain disease in living brain
An experimental positron emission tomography (PET) tracer is effective in diagnosing concussion-related brain disease while a person is still alive.

Recruiting bacteria to be technology innovation partners
For most people biofilms conjure up images of slippery stones in a streambed and dirty drains.

Drug's effect on Alzheimer's may depend on severity of disease
A cancer drug that has shown promise against Alzheimer's disease in mice and has begun early clinical trials has yielded perplexing results in a novel mouse model of AD that mimics the genetics and pathology of the human disease more closely than any other animal model.

Decoding 'sweet codes' that determine protein fates
We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects.

Researchers find neural compensation in people with Alzheimer's-related protein
The human brain is capable of a neural workaround that compensates for the buildup of beta-amyloid, a destructive protein associated with Alzheimer's disease, according to a new study led by researchers at the University of California, Berkeley.

Vitamin E intake critical during 'the first 1,000 days'
Amid conflicting reports about the need for vitamin E and how much is enough, a new analysis published today suggests that adequate levels of this essential micronutrient are especially critical for the very young, the elderly, and women who are or may become pregnant.

Compound protects brain cells after traumatic brain injury
A new class of compounds has now been shown to protect brain cells from the type of damage caused by blast-mediated traumatic brain injury (TBI).
More Alzheimer's Disease Current Events and Alzheimer's Disease News Articles

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...

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...

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. ...

Alzheimer's Disease: Targets for New Clinical Diagnostic and Therapeutic Strategies (Frontiers in Neuroscience)

Alzheimer's Disease: Targets for New Clinical Diagnostic and Therapeutic Strategies (Frontiers in Neuroscience)
by Renee D. Wegrzyn (Editor), Alan S. Rudolph (Editor)


In recent years, a tremendous amount of effort has been focused on better understanding the fundamentals of Alzheimer’s disease (AD) to facilitate early and accurate diagnosis and appropriately targeted therapeutic treatments. Alzheimer’s Disease: Targets for New Clinical, Diagnostic, and Therapeutic Strategies provides a detailed synopsis of the current state of the art of diagnostics and therapeutics and identifies emerging technologies and molecules that show promise in the management and treatment of AD. With contributions from experts drawn from academia, clinical practice, and the biotechnology and pharmaceutical industries, the book explores: The basis of AD and the role of Aβ oligomers in development of disease Existing and emerging in vitro biomarker-based methodologies...

A Caregiver's Guide to Alzheimer's Disease: 300 Tips for Making Life Easier

A Caregiver's Guide to Alzheimer's Disease: 300 Tips for Making Life Easier
by Patricia R. Callone (Author), Connie Kudlacek (Author), Barabara C. Vasiloff (Author), Janaan Manternach (Author), Roger A. Brumback (Author)


An estimated 5 million Americans have Alzheimer's disease. That number continues to grow - by 2050 the number of individuals with Alzheimer's could range from 11.3 million to 16 million. Alzheimer's disease is not a normal part of aging. It is a devastating disorder of the brain's nerve cells that impairs memory, thinking, and behavior. Written for patients, their families, and caregivers, A Caregiver's Guide to Alzheimer's Disease: 300 Tips for Making Life Easier will help readers understand what is physically happening to the brain so they can empower their own special skills and talents throughout the disease process. The book is divided into three sections that correspond to the progression of Alzheimer's and the unique challenges encountered at each stage.Section A: The major part of...

Where Two Worlds Touch: A Spiritual Journey Through Alzheimer's Disease

Where Two Worlds Touch: A Spiritual Journey Through Alzheimer's Disease
by Jade C. Angelica (Author)


Jade Angelica shares the wisdom and hope she gleaned from caring for her mother and from many years working closely with Alzheimer's patients and caregivers. Challenging the predominant belief that people with Alzheimer's no longer have purpose, potential, or the capacity for meaningful relationship, Where Two Worlds Touch is both a spiritual memoir and a pastoral guide for those who love someone with Alzheimer's. Readers will find here the reassuring words of a friend who has been there and can give advice on preserving connection, finding hope, self-care, and staying open to the possibility of grace.

Alzheimer's Disease and Other Dementias - The Caregiver's Complete Survival Guide

Alzheimer's Disease and Other Dementias - The Caregiver's Complete Survival Guide
by Nataly Rubinstein (Author)


As a caregiver, you face challenging situations and conflicting information concerning diagnoses, treatments, coping with everyday activities, and dementia itself. This easy-to-read book will give you the resources to make informed decisions regarding the best possible care for you and your loved one. Written by a licensed clinical social worker with twenty-five years of experience, Alzheimer's Disease and Other Dementias: The Caregiver's Complete Survival Guide offers tips on:
- Getting the best treatment for your loved one
- Handling difficult behaviors
- Making the home safer
- Choosing respite and long-term care options
- Finding legal and financial assistance
- Improving overall quality of life Drawing from clinical and personal experience, Nataly Rubinstein...

The Memory Cure : How to Protect Your Brain Against Memory Loss and Alzheimer's Disease

The Memory Cure : How to Protect Your Brain Against Memory Loss and Alzheimer's Disease
by Majid Fotuhi (Author), Peter V. Rabins (Foreword)


A Proven Plan for Protecting Your Memory--At Any Age, At Any TimeYou've probably taken steps to protect your finances, your health, and your family. Isn't it time to protect your memories? Science is exploding with new discoveries related to the brain, aging, and memory--discoveries that prove the actions you take today impact your memory for decades to come. Dr. Majid Fotuhi, one of the foremost experts in memory loss and Alzheimer's disease, outlines an action plan to improve mental agility and prevent memory loss. The Memory Cure includes:A dynamic 10 step memory protection planEncouraging updates in the field of cognitive researchThe truth behind popular beliefs about memory loss and agingA comprehensive resource section including information about clinical...

© 2014 BrightSurf.com