New drug could be the first to prevent the progression of Alzheimer's disease
By Darren Quick
December 18, 2011
Anyone who has watched as Alzheimer's disease robs a friend or family member of their memories and faculties before ultimately claiming their life knows just what a truly horrible disease it is. According to the World Health Organization, it is the fourth leading cause of death in high-income countries and, due to an aging worldwide population, it is predicted to affect one in 85 people worldwide by 2050 - unless a treatment can be found. Scientists at the Salk Institute for Biological Studies have high hopes for a new drug they have developed that has improved memory and prevented brain damage in mice and is a promising candidate for the first drug capable of halting the progression of Alzheimer's in humans.
Although scientists have as yet been unable to pin down the causes and progression of Alzheimer's, research indicates it is associated with amyloid plaques and neurofibrillary tangles in the brain. For this reason, much of the search for a treatment by the pharmaceutical industry has focused on the biological pathways involved in the formation of amyloid plaques. However, to date, all amyloid-based drugs have failed in clinical trials.
The Salk team decided to take a different approach by developing methods for using living neurons grown in laboratory dishes to test the effectiveness of new synthetic compounds in protecting the brain cells against several pathologies associated with brain aging. Starting with a lead compound originally developed for the treatment of stroke and traumatic brain injury and guided by test results from each chemical iteration of the compound, the team says they were able to alter its chemical structure to make a much more potent Alzheimer's drug, known as J147.
"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," says Marguerite Prior, a research associate, who led the project along with Qi Chen, a former Salk postdoctoral researcher, working in Salk's Cellular Neurobiology Laboratory headed by David Schubert. "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."
Testing the promising compound as an oral medication in mice, the team, working with Amanda Roberts, a professor of molecular neurosciences at The Scripps Research Institute, conducted a range of behavioral tests that showed that the drug improved memory in normal rodents.
Further testing showed that the compound prevented brain damage 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 involved in memory formation that helps support the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses.
"J147 enhances memory in both normal and Alzheimer's mice and also protects the brain from the loss of synaptic connections," said Schubert. "No drugs on the market for Alzheimer's have both of these properties."
The team says J147 could be tested for treatment of Alzheimer's in humans in the near future and, because of its broad ability to protect nerve cells, may also be effective for treating other neurological disorders, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS), as well as stroke.
Schubert and Prior outline their team's research in the video below.
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