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Neurogenetic studies show proprietary compound reduces brain plaques linked to Alzheimer's
Date:9/9/2010

he work published in Neuron is the first to describe these mechanistically and biochemically distinct GSM compounds and how they provide a more selective mechanism than GSIs. The key advantages of these small molecules include reduction of the "toxic" form of beta amyloid (Aβ42), direct binding to components of the gamma secretase complex, and excellent brain exposure. The paper demonstrated that Neurogenetic Pharmaceuticals' approach of gamma secretase modulation allows for selective reduction of Aβ42 and amyloid pathology. Oral administration of NGP 555 (identified as compound 4 in Neuron) in transgenic AD mice resulted in a dose-related lowering of both plasma and brain Aβ42. Chronic daily administration for 7 months led to significant reduction in both diffuse and neuritic plaques, without the GI-related side effects found with GSI compounds, according to the paper in Neuron. The work, conducted by researchers at TorreyPines Therapeutics (TPTX) in collaboration with academic institutions, concludes that these types of GSM compounds warrant further investigation as a potentially safe and effective approach for prevention of AD.

"This study links A biomarker and pathology findings with a mechanistic understanding of how our compounds selectively target a key enzyme involved in the pathology of Alzheimer's disease," said Maria Z. Kounnas, Ph.D., lead author on the study and vice president of Alzheimer's Research at NGP. "Combining early disease identification with a treatment capable of preventing AD-related pathology, such as NGP 555, would represent an important advance in our ability to prevent AD or hinder its progression to dementia. Clearly, the earlier AD is detected and treated, the better the likelihood of a good outcome."


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