10/16 Conference Call/Webinar: Update on DS Cognition Research & Clinical Trials

Register today! Wed, Oct 16, 2013  1:00 pm ET/10:00 am PT Cost: Free This webinar brought to you by: Down Syndrome Affiliates in Action and Down Syndrome Research and Treatment Foundation The Research Landscape: Update on DS Cognition Research and Ongoing Clinical Trials Available to Nonmembers!  Down syndrome cognition research holds enormous potential for people with Ds — but have your members heard? This webinar will give affiliate leaders and members of the Down syndrome community the information families need about how science is working to deliver increased opportunity, independence, and fulfillment to individuals with Down syndrome. Researchers are making great strides towards delivering improved learning, memory and speech, and towards preventing the additional cognitive decline people with Ds experience as they age. Find out about this progress, including ongoing clinical trials, when we detail recent significant advances in the field of Down syndrome cognition research in this free online discussion. This informative, accessible presentation is designed specifically to prepare you with accurate, up-to-date information, and will cover: How to communicate the latest research advances and their significance for individuals with Down syndrome in enhancing their daily lives; How the Down syndrome community is essential to achieving successful new therapies, and what you can do to get involved; How participation by individuals with Down syndrome benefits not only people with Ds but also benefits those in the broader community; How working together to leverage support can significantly increase funding for Down syndrome research, and speed the development of safe, effective therapies to improve quality of life for people with Ds. We hope you will join us for this free webinar to help you learn more about the significant advances and exciting progress that is currently underway.  Register today:  https://dsaia.clickwebinar.com/The_Research_Landscape/register?lang=en

Neuron Finding Lifts Hopes for Down Syndrome Drug

from Joan Arehart-Treichel, Psychiatric News:

Discovering a dearth of acetylcholine and norepinephrine in the hippocampus of a mouse model of Down syndrome opens promising therapeutic avenues for people with the disorder.

Down syndrome is usually due to each cell in the human body having three copies, rather than two copies, of chromosome 21. This heartbreaking illness leads not just to a spate of physical abnormalities and cognitive dysfunction, but often to early-onset Alzheimer’s disease.

A pivotal brain region affected by Down syndrome is the hippocampus. Now scientists at Stanford University School of Medicine have made two important findings about what occurs in that region in a mouse model of Down syndrome, which purportedly translates to people with the syndrome.

 

One is a loss of two types of neurotransmitter-producing neurons in the hippocampus—acetylcholine-producing neurons and norepinephrine-producing neurons. The other is that this loss is linked with the overexpression of the amyloid precursor protein gene in the hippo-campus. Mutations in this gene, which is located on chromosome 21, are known to lead to early-onset Alzheimer’s, and it may be that early onset of Alzheimer’s pathology in people with Down syndrome is due in part to overexpression of the amyloid precursor protein gene.

 

These findings have provocative therapeutic implications for people with Down syndrome, the scientists also pointed out online September 27 in Biological Psychiatry. For instance, although the amyloid precursor protein gene should be a primary therapeutic target in Down syndrome, there are no safe and effective medications on the market to reduce the gene’s expression. In contrast, since a paucity of norepinephrine-producing neurons in the hippo-campus also seems to contribute to Down syndrome, medications that enhance norepinephrine levels in the brain and are already on the market to treat attention-deficit/hyperactivity disorder might be of therapeutic benefit to individuals with Down syndrome.

 

Moreover, such medications might also subdue the action of the amyloid precursor protein gene in such individuals, they speculated.

 

“We are indeed working on this group of drugs—drugs that are able to increase norepinephrine levels and that have already been approved by the Food and Drug Administration—in our mouse models,” Ahmad Salehi, M.D., Ph.D., a clinical associate professor of psychiatry at Stanford and the study’s senior investigator, told Psychiatric News. “This strategy could speed up the development of a treatment for cognitive function in Down syndrome enormously.”

 

The scientists’ discovery of a paucity of acetylcholine-producing neurons in the hippocampus of an animal model of Down syndrome holds therapeutic promise, the researchers noted. In fact, other researchers reported eight years ago that the Alzheimer’s drug donepezil, which slows the break down of acetylcholine in the brain, might improve cognitive scores and expressive language in children and adults with Down syndrome.

 

Yet if donepezil improves cognitive function and language in these individuals, is there reason to believe that medications that increase norepinephrine would be superior to donepezil in that regard? Asalehi believes there is. “I think using norepinephrine-ergic drugs would be far superior to cholinergic ones for the following reasons: The norepinephrine system has some regulatory effects on the cholinergic one. It has been shown that lesions in the former lead to increased severity of cholinergic deficits; most adults with Down syndrome will show Alzheimer’s-related pathology, particularly amyloid plaques. There are new studies showing that increasing norepinephrine levels in mouse models of Alzheimer’s significantly reduce amyloid accumulation. These findings suggest that using norepinephrine-ergic drugs might not only restore cognition in kids with Down syndrome, but also reduce Alzheimer’s-related pathology in adults with the syndrome.”

 

“Studies such as this one help to further our overall understanding of central nervous system function and in particular differences seen in individuals with Down syndrome,” Melanie Manning, M.D., director of the Center for Down Syndrome at Stanford’s Lucile Packard Children’s Hospital, told Psychiatric News.

 

“Many of the families of individuals with Down syndrome follow results from research studies such as this one with great interest. They express a desire to learn more about potential clinical applications that lie ahead.”

 

The research was funded by the Mental Illness Research, Education, and Clinical Center Department of Veterans Affairs; Down Syndrome Research and Treatment Foundation; Thrasher Foundation; and Alzheimer’s Association.

 

Ahmad Salehi, M.D., Ph.D.: 

 

An abstract of “Neurobiological Elements of Cognitive Dysfunction in Down Syndrome: Exploring the Role of APP” is posted at <www.biologicalpsychiatryjournal.com/article/S0006-3223(11)00822-5/abstract>.

Scientist tests promising drug on those with Down syndrome

from Health Canal:

A University of Colorado School of Medicine scientist is finishing a major clinical trial on a drug that could boost cognitive function in those with Down syndrome, significantly improving their quality of life and representing a potential milestone in research on this genetic disorder.

“We are hoping to enhance memory and learning in those with Down syndrome,” said Alberto Costa, MD, Ph.D., an associate professor of medicine and the neuroscientist leading the effort.

“We have been studying this drug for three years and are now ready to analyze the data on our trial. Our team at the University of Colorado and Children’s Hospital Colorado expects to have the results in the next two or three months.”

Costa, whose work was chronicled in last Sunday’s New York Times Magazine, (A Drug for Down Syndrome), is tested the drug memantine, currently used to relieve symptoms of Alzheimer’s disease, in 39 people with Down syndrome. About half received the drug and the others a placebo. In 2007, Costa demonstrated that memantine could improve memory function in mice with Down syndrome.

And now, for the first time, he is taking a drug effective in the treatment of learning and memory deficits in mice with Down syndrome and applying it to humans, a move described by the New York Times as “a milestone in the history of Down syndrome research.”

Costa is no disinterested researcher, his 16-year-old daughter Tyche – named for the Greek goddess of Fortune - has Down syndrome. Like others with the condition, she faces the specter of a steady decline in mental functioning as she gets older and a roughly 20 percent chance of getting Alzheimer’s in her 50’s. After that diagnosis, death is often just five years away.

“I feel I am racing the clock to find something that will at least keep her functioning at the level she is at now,” Costa said. “As they age, parts of their brain will shrink and their functions will diminish.”

Costa is actively pursuing links between Down and Alzheimer’s disease. He says babies born with Down often carry the biological markers for Alzheimer’s.

“They have the disease from the get go,” he said.

Costa says the world is awash in false assumptions about Down syndrome ranging from distortions on life expectancy to educational limitations. In fact, depending on the severity of their condition, those with Down can live into their 70s, attend college, live independently and hold down jobs.

 

“If we are successful, it will increase hope and expectations for those with Down syndrome,” Costa said. “Right now there are drugs for the signs and symptoms of medical conditions more frequent in those with Down syndrome, but nothing to improve brain function. In fact, the prevailing wisdom has been that there is essentially nothing you can do to boost memory and learning in this group. Hopefully, we can prove them wrong.”

But he and other Down researchers face an overall lack of federal funding, especially when compared to other diseases and disorders.

Costa has been supported by Forest Pharmaceuticals which is funding the clinical trial, the Linda Crnic Institute for Down Syndrome, the Coleman Institute for Cognitive Disabilities at the University of Colorado and the National Institute of Child Health and Development, part of the National Institutes of Health.

“Clearly these funding sources are the unsung heroes,” Costa said. “They may not get the attention or publicity but I can assure you that our efforts and the future of those with Down syndrome would be seriously compromised without their continued generosity.”

Drug may reverse Down syndrome symptoms

from mother nature network:

 

Dr. Alberto Costa has a personal stake in his Down syndrome research: his daughter, Tyche.

 

Costa's life and work changed direction after she was born 16 years ago and Costa — a physician and neuroscientist — decided to dedicate his career to the study of Down syndrome.In the past decade and a half, Costa's research has focused on normalizing the brain cells in the hippocampus, the portion of the brain responsible for memory and spatial navigation.

 

In 2006, Costa published a study that found that a drug — the antidepressant Prozac — could normalize the cells in this area of the brain. But it was still unclear whether or not these normalized cells would automatically translate to better memory and improve cognitive deficits.

 

The next year, Costa worked with Down syndrome mice and found that the Alzheimer’s drug memantine could improve their memory. Costa's study showed that a single injection of memantine produced benefits within minutes, enabling Down-equivalent mice to learn as well as standard mice.

 

Costa's theory is that memantine works not by increasing or changing brain cells, but by normalizing how they work. People with Down syndrome have three copies of all or most of the genes on Chromosome 21 instead of just two, so receptors in this area of the brain tend to be hyperactive — overreacting to stimuli and making it difficult for the brain to focus and learn.

 

Memantine, according to Costa's hypothesis, quiets the noise, allowing the brain cells to react normally. Costa's journey was the focus of a feature story in this Sunday's New York Times Magazine.

 

Now Costa is working on the first randomized clinical trial to use the drug in humans. For Costa's trail, he is testing memory and spatial learning in 40 young adults with Down syndrome who have received memantine pills daily for 16 weeks. Costa will present preliminary results of this research at a scientific meeting in Illinois this fall. If successful, memantine could provide a new future for Costa's daughter Tyche and the 400,000 other people living with Down syndrome in the U.S.