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


Leaky blood-brain barrier linked to Alzheimer's disease
Researchers using contrast-enhanced MRI have identified leakages in the blood-brain barrier (BBB) of people with early Alzheimer's disease (AD), according to a new study published online in the journal Radiology.

Vicious circle of platelets
They were published in the current issue of the renowned journal "Science Signaling". The scientists provide evidence for the first time that treatment of Alzheimer transgenic model mice with an anti-platelet drug leads to significantly reduced amyloid plaques in cerebral vessels.

Study paves way for new therapies in fight against calcium disorders
A study led by researchers at Georgia State University provides new insights into the molecular basis of human diseases resulting from mutations in the calcium-sensing receptor (CaSR), a protein found in cell membranes.

Ancient anti-inflammatory drug salicylic acid has cancer-fighting properties
Scientists from the Gladstone Institutes have identified a new pathway by which salicylic acid--a key compound in the nonsteroidal anti-inflammatory drugs aspirin and diflunisal--stops inflammation and cancer.

The deadly toxin acrolein has a useful biological role
Scientists from RIKEN in Japan have discovered that acrolein--a toxic substance produced in cells during times of oxidative stress--in fact may play a role in preventing the process of fibrillation, an abnormal clumping of peptides that has been associated with Alzheimer's disease and other neural diseases.

Researchers identify immune genes tied to common, deadly brain cancer
Researchers have identified a group of immune system genes that may play a role in how long people can live after developing a common type of brain cancer called glioblastoma multiforme, a tumor of the glial cells in the brain.

Can Alzheimer's disease-associated peptide fight bacterial infection?
Amyloid-ß is a sticky peptide notorious for forming destructive plaques in the brains of Alzheimer's disease patients, but a new study suggests that it may also serve a protective function as an antimicrobial peptide.

Human amyloid-beta acts as natural antibiotic in the brains of animal models
A new study from Massachusetts General Hospital (MGH) investigators provides additional evidence that amyloid-beta protein - which is deposited in the form of beta-amyloid plaques in the brains of patients with Alzheimer's disease - is a normal part of the innate immune system, the body's first-line defense against infection.

Progranulin and dementia -- a blood sample does not tell the full story!
Progranulin is a central protein in both neuronal survival and neurodegenerative diseases. It is thus not surprising that altered progranulin levels represent a universal theme shared across several common neurodegenerative diseases.

PET imaging with special tracer can detect and diagnose early Alzheimer's disease
The effort to find ways to detect and diagnose preclinical Alzheimer's disease (AD) has taken a big step forward with the use of positron emission tomography (PET), a "nuclear medicine" for imaging processes in the body, when PET is used with a special 'tracer' that binds to the amyloid plaques in the brain that are a characteristic cause of AD.
More Alzheimer's Disease Current Events and Alzheimer's Disease News Articles

Alzheimer's Disease: What If There Was a Cure?: The Story of Ketones

Alzheimer's Disease: What If There Was a Cure?: The Story of Ketones
by Mary T Newport (Author)


In this second edition Dr. Newport, a neonatal practitioner, continues the story of Steve's progress and provides the most recent research on such topics as possible causes of Alzheimer's due to the herpes simplex virus and nitrosamine substances and how infection, inflammation and genetic makeup may affect an individual's response to fatty acid therapy.

Outsmarting Alzheimer's: What You Can Do To Reduce Your Risk

Outsmarting Alzheimer's: What You Can Do To Reduce Your Risk
by Kenneth S. Kosik (Author)


An easy-to-follow, research-based guide to the simple, low-cost choices that give the reader the power to reduce the risk of developing Alzheimer's disease and dementia; slow the progression of the disease; and mitigate symptoms and improve well-being.

Did you know that getting on the treadmill can help keep your brain sharp? Or that repeatedly staying up to catch the late show could increase the likelihood of being struck down by dementia? The dozens of choices you make over the course of any average day—ordering the curry versus the burger with fries, taking the stairs versus the elevator—all add up. Together with your family history, they establish your chances of getting Alzheimer’s years from now. No drugs or procedures can cure or even effectively treat Alzheimer’s...

Developing Therapeutics for Alzheimer's Disease: Progress and Challenges

Developing Therapeutics for Alzheimer's Disease: Progress and Challenges
by Michael S. Wolfe PhD (Editor)


Developing Therapeutics for Alzheimer's Disease: Progress and Challenges provides a thorough overview of the latest advances toward the development of therapeutics for Alzheimer’s disease, along with the major hurdles that still must be overcome and potential solutions to these problems. Despite the lack of progress toward developing therapeutics that can slow or stop the progression of this disease, important discoveries have been made and many promising approaches are advancing in preclinical studies and clinical trials. This book outlines the special challenges related to specific targets and approaches, while presenting a realistic, comprehensive and balanced view of drug discovery and development in this area. Written by international leaders in the field, the book assesses...

The Alzheimer's Prevention & Treatment Diet

The Alzheimer's Prevention & Treatment Diet
by Richard S. Isaacson MD (Author), Christopher N. Ochner PhD (Author)


Alzheimer s disease (AD) is a type of dementia that can be very hard for both the patient and the caregiver. Currently, five million Americans have been diagnosed with AD--and that number is likely to triple by 2050. While the cause of Alzheimer s disease is still a mystery, new research has increased our knowledge of certain aspects of the disease. Perhaps most significant, studies show that proper diet may make a real difference, not only in slowing the progression of AD, but also in preventing it. In this groundbreaking book, a notable expert on Alzheimer s disease has teamed up with a leading researcher of nutrition to create a unique guide to understanding and managing this serious condition. The Alzheimer s Prevention & Treatment Diet outlines a cutting-edge nutritional program that...

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. ...

The Best Friends Approach to Alzheimer's Care

The Best Friends Approach to Alzheimer's Care
by Virginia Bell (Author), David Troxel (Author)


Presentation of a model of care for Alzheimer's patients stressing empathy and friendship, for nurses, adult day center staff, and families of patients. Emphasizes the positive aspects of situations involving Alzheimer's care rather than patients' victimization. Softcover.

Going Gentle Into That Good Night: A Practical and Informative Guide For Fulfilling the Circle of Life For Our Loved Ones with Dementias and Alzheimer?s Disease

Going Gentle Into That Good Night: A Practical and Informative Guide For Fulfilling the Circle of Life For Our Loved Ones with Dementias and Alzheimer?s Disease
by Ms. Sandra Ross (Author)


This book is written to give practical and real-world help to those us responsible for the care of loved ones with dementias and Alzheimer's Disease.

It's not like all those other books. Believe me, I found most of them to be a waste of my time because they were not hands-on and accessible and they didn't tell me the stuff I really needed to know and had to learn on my own.

If you want a lot of theory, this is not the book for you. If you want to read one more book that talks about dementias and Alzheimer's Disease from a high-level and clinical standpoint, this book is not for you.

But you want the succinct and practical experience and advice from somebody who's walked your shoes as when I cared for my mom, this book is for you.

I wish there had been one...

Alzheimer's Disease: What If There Was a Cure?: The Story of Ketones

Alzheimer's Disease: What If There Was a Cure?: The Story of Ketones
by Mary T Newport (Author)


Acting on 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, author Dr. Mary T. Newport has demonstrated through her care for her husband that there is hope, relief, and perhaps a cure.

Learning to Speak Alzheimer's: A Groundbreaking Approach for Everyone Dealing with the Disease

Learning to Speak Alzheimer's: A Groundbreaking Approach for Everyone Dealing with the Disease
by Joanne Koenig Coste (Author), Robert Butler (Foreword)


More than four million Americans suffer from Alzheimer’s, and as many as twenty million have close relatives or friends with the disease. Revolutionizing the way we perceive and live with Alzheimer’s, Joanne Koenig Coste offers a practical approach to the emotional well-being of both patients and caregivers that emphasizes relating to patients in their own reality. Her accessible and comprehensive method, which she calls habilitation, works to enhance communication between carepartners and patients and has proven successful with thousands of people living with dementia. Learning to Speak Alzheimer’s also offers hundreds of practical tips, including how to · cope with the diagnosis and adjust to the disease’s progression · help the patient talk about the illness · face the...

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...

© 2016 BrightSurf.com