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Gamma Secretase Modulators Show Promise in Alzheimer's Disease Animal Model Efficacy Studies, According to Research Conducted by TorreyPines Therapeutics
Date:3/31/2008

LA JOLLA, Calif., March 31 /PRNewswire/ -- Gamma secretase modulators (GSMs) have shown promise in Alzheimer's disease animal model efficacy studies, according to research conducted by TorreyPines Therapeutics, Inc. (Nasdaq: TPTX).

Presented by Steven Wagner, Ph.D., the company's Chief Scientific Officer, at the recent Keystone Symposium on Alzheimer's Disease, data demonstrated that GSMs provide a more selective mechanism than gamma secretase inhibitors (GSIs). The in vivo research involved internally discovered and optimized compounds that modulate the g-secretase complex without inhibiting its catalytic activity. These GSMs appear to reduce the formation of the longer pathogenic Ab peptides (e.g, Ab42) and allow the g-secretase enzyme complex to generate the shorter, less fibrillogenic Ab peptides such as Ab38 and Ab37 and to perform its other necessary functions.

"We have identified a series of GSM compounds that are intended to modulate the enzyme's activity without preventing it from performing its normal functions," said Dr. Wagner. "These orally bio-available, small molecule GSMs appear to have addressed some of the pitfalls associated with the GSI compounds, which have been associated with side effects. The significance of our findings is that we may be able to selectively attenuate the pathological functions of this enzyme complex without affecting the other critical physiological functions it performs."

The major pathological hallmark of Alzheimer's disease is the abundance of deposits called neuritic plaques in key areas of the brain that control memory and cognition. These neuritic plaques are largely comprised of aggregations of fibrillar peptides referred to as amyloid b, or Ab peptides. Evidence indica
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SOURCE TorreyPines Therapeutics, Inc.
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