Successful reduction in the levels of aggregated Abeta with GSMs

Dec 9 2009

EnVivo Pharmaceuticals today reported the successful reduction in the levels of aggregated Abeta or Beta-Amyloid in an aged transgenic model (Tg2576) of Alzheimer's disease with its lead gamma-secretase modulator (GSM) EVP-0962. The aggregated Abeta, containing predominately oligomeric and larger Abeta fibrillar species, is considered to be the toxic entity in Alzheimer's disease. The reduction of these aggregates further supports the disease modifying potential of EVP-0962 as reported in previous studies.

GSMs are a new generation of potential Alzheimer drugs. The proprietary small molecule EVP-0962 selectively inhibits the production of the toxic Abeta42 peptide without affecting the total amount of Abeta. As EVP-0962 does not affect other gamma secretase substrates required for normal function, such as Notch, it is predicted to slow the progression of Alzheimer's disease by reducing the disease-associated toxic Abeta42 species and to display an intrinsically superior safety profile compared to gamma secretase inhibitors (GSIs).

The study results were obtained as part of a collaborative effort with Amorfix Life Sciences, using its A4 Assay for the quantitative detection of aggregated Abeta. The A4 Assay can detect accumulation of Abeta in standard Alzheimer's disease animal models several months before conventional microscopic procedures thereby accelerating the preclinical screening of new drugs for Alzheimer's disease. A4 is significantly more sensitive than current methods for detecting toxic oligomers and amyloid and can be used in high-throughput applications. The data independently confirmed previously reported results (International Conference on Alzheimer's Disease 2009, Vienna, and Society for Neuroscience 2009, Chicago) by EnVivo that demonstrated potent Abeta42 lowering and concomitant positive effects on cognition in the Tg2576 model. The selective decrease in Abeta42 and now the reduction of the aggregated Abeta further demonstrates that EVP-0962 is a potent GSM.