Tuesday, January 3, 2012

New drug may stop the progression of Alzheimer's disease

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Medical News Today

According to findings in a study published in PLoS One, a new drug candidate may be the first drug that is capable of halting the devastating mental decline of Alzheimer's disease. Researchers administered the drug, known as J147, to mice with Alzheimer's disease and observed an associated improvement in memory and prevention in brain damage. The new drug was developed by scientists at the Salk Institute for Biological Studies, led by David Schubert, and could be trialled as a treatment for Alzheimer's disease in humans in the near future.

David Schubert, head of Salk's Cellular Neurobiology Laboratory, explained:

"J147 enhances memory in both normal and Alzheimer's mice and also protects the brain from the loss of synaptic connections. No drugs on the market for Alzheimer's have both of these properties."


The researchers say that even though the new compound's efficacy and safety in humans has not yet been established, the results indicate that the drug could become a potential treatment in people with Alzheimer's. 



 According to figures of the National Institutes of Health, a staggering 5.4 million Americans suffer from Alzheimer's. The Alzheimer's Association estimates that by 2050 more than 16 million will be affected by the disease, resulting in annual medical costs of over $1 trillion. 


Alzheimer's causes a steady, irreversible decline in brain function. Affected individuals experience a progressive loss of memory and ability to think clearly, which subsequently leads to the person being unable to perform simple tasks, such as eating and talking, and ultimately ends in death.

Alzheimer's is associated with aging, with a typical onset in individuals aged 60 years or above, although a small percentage of families carry a genetic risk for earlier onset. Amongst the top ten causes of mortality, Alzheimer's is the only disease that cannot be prevented, cured or reduced to progress slowly.

Onset of Alzheimer's seems to be influenced by a complex mixture of genetics, lifestyle factors and environment, although scientists still remain unclear what causes the disease. Until now, drugs developed for the treatment of Alzheimer's, such as Aricept, Razadyne and Exelon have only produced short periods of memory improvements, yet do not halt the overall progression of the disease.

Schubert and his team set out to find a new type of drug, but instead of following the current trend of the pharmaceutical industry, they decided to take a different approach. The pharmaceutical industry seems to focus exclusively on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein, which characterize the disease, but according to Schubert, until now, all amyloid-based drugs have failed in clinical trials.

Instead, they developed methods in which they used living neurons grown in laboratory dishes to assess the probability of whether or not new synthetic compounds prove effective in protecting the brain cells against several pathologies connected with brain aging. Based on the test results from each chemical iteration of the lead compound, a test originally designed for treating stroke and traumatic brain injuries, Schubert and his team managed to alter its chemical structure to produce a much more potent Alzheimer's drug. 



Marguerite Prior, a research associate in Schubert's lab, who led the project together with Qi Chen, a former Salk postdoctoral researcher, explained:

"Alzheimer's is a complex disease, but most drug development in the pharmaceutical world has focused on a single aspect of the disease - the amyloid pathway. In contrast, by testing these compounds in living cell cultures, we can determine what they do against a range of age-related problems and select the best candidate that addresses multiple aspects of the disease, not just one."




 The researchers subsequently tested their promising J147 compound as an oral medication in mice. In collaboration with Amanda Roberts, a professor of molecular neurosciences at The Scripps Research Institute, they performed a series of behavioral tests, which demonstrated that the drug improved memory in normal rodents. 


They subsequently demonstrated that J147 prevented cognitive decline in animals with Alzheimer's and also proved that mice and rats treated with the drug produced more of a protein called brain-derived neurotrophic factor (BDNF). BDNF is a molecule involved in memory formation and protects neurons from toxic insults. It also helps in the growths of new neurons and connects with other brain cells.

According to the researchers, based on the compounds broad ability to protect nerve cells, J147 may also be effective in the treatment of other neurological disorders, including Parkinson's and Huntingdon's disease as well as amyotrophic lateral sclerosis (ALS), and stroke.

The research was supported through funding by the Fritz B. Burns Foundation, the National Institutes of Health, the Bundy Foundation and the Alzheimer's Association.

Written by Petra Rattue

View drug information on ARICEPT; Exelon.

Copyright: Medical News Today

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