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Targeting a key enzyme with gene therapy reversed course of Alzheimer's disease in mouse models

In mice, that had been genetically engineered to develop Alzheimer's disease, scientists were able to reverse the rodents' memory loss by reducing the amount of an enzyme that is crucial for the development of Alzheimer's disease.

"What we are showing is a proof of principle that stopping the synthesis of a protein that is necessary for the formation of the telltale plaques reverses the progression of the disease, and more importantly, the cognitive function of these mice, which had already been impaired, has now recovered," says Inder Verma, professor in the Laboratory for Genetics at the Salk Institute for Biological Studies.

The findings, which are the result of a close collaboration between researchers at the Salk Institute and scientists at the University of California in San Diego, are reported in an advance on-line publication of Nature Neuroscience.

In the past, gene therapy has been mainly used to deliver normal genes into cells to compensate for defective versions of the gene causing disease. In their study, the researchers used gene therapy to silence a normally functioning gene. Exploiting a mechanism called RNA interference, they were able to turn down the gene that helps produce the characteristic amyloid plaques that are one of the hallmarks of Alzheimer's disease.

"Within a month of treatment, mice that had already suffered memory deficits could learn and remember how to find their way through a water maze," says co-author Robert Marr, a post-doctoral researcher in Verma's lab.

"It appears that these mice can come back from a very severe level of disease progression," adds first author Oded Singer, also at the Salk. "This is a very important finding because humans are usually diagnosed when the disease has already progressed relatively far."

But he warns that it is too early to make direct comparisons with the human disease, since mice ordinarily don't develop the symptoms of the disease unless they are
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Contact: Cathy Yarbrough
yarbrough@salk.edu
858-453-4100 x 1290
Salk Institute
20-Sep-2005


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