Sunday 20 April, 2014

New Alzheimer’s drug may help prevent disease progression

Published On: Thu, Dec 15th, 2011 | Alzheimer's | By BioNews

A new drug candidate that may be the first capable of halting the devastating mental decline of Alzheimer’s disease has been developed by scientists.

The disease causes a steady, irreversible decline in brain function, erasing a person’s memory and ability to think clearly until they are unable to perform simple tasks such as eating and talking, and it is ultimately fatal.

Alzheimer’s is linked to aging and typically appears after age 60, although a small percentage of families carry a genetic risk for earlier onset. Among the top ten causes of death, Alzheimer’s is the only one without a way to prevent, cure or slow disease progression.

J147, developed by researchers at the Salk Institute for Biological Studies, when given to mice with Alzheimer’s improved memory and prevented brain damage caused by the disease.

The drug could be tested for treatment of the disease in humans in the near future.

“J147 enhances memory in both normal and Alzheimer’s mice and also protects the brain from the loss of synaptic connections,” David Schubert, whose team developed the drug, said.

“No drugs on the market for Alzheimer”s have both of these properties,” he said.

Although it is yet unknown whether the compound will prove safe and effective in humans, researchers claim that their results suggest the drug may hold potential for treatment of people with Alzheimer’s.

To find the new type of drug, Schubert and his colleagues bucked the trend within the pharmaceutical industry of focusing exclusively on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease.

According to Schubert, to date all amyloid-based drugs have failed in clinical trials.

Instead, the Salk team developed methods for using living neurons grown in laboratory dishes to test whether or not new synthetic compounds were effective at protecting the brain cells against several pathologies associated with brain aging.

Based on the test results from each chemical iteration of the lead compound, which was originally developed for treatment of stroke and traumatic brain injury, they were able to alter its chemical structure to make a much more potent Alzheimer”s drug.

“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,” Marguerite Prior, who led the project along with Qi Chen, said.

“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,” Prior said.

With a promising compound in hand, the researchers shifted to testing J147 as an oral medication in mice. Working with Amanda Roberts, a professor of molecular neurosciences at The Scripps Research Institute, they conducted a range of behavioural tests that showed that the drug improved memory in normal rodents.

They went on to show that it prevented cognitive decline in animals with Alzheimer’s and that mice and rats treated with the drug produced more of a protein called brain-derived neurotrophic factor (BDNF), a molecule that protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation.

The study has been recently published in PloS One.

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