![]() The Merck samples came from a Phase 3 trial, while the others came from Phase 2s. In Amsterdam, Stefan Lichtenthaler, Technical University of Munich, reported analysis of cerebrospinal fluid samples taken at baseline and after treatment with three different BACE inhibitors, Merck’s verubecestat, Novartis’s umibecestat, and Shionogi’s atabecestat. What has changed is that scientists now have a way to identify and monitor at least some of those cleavages. Many are found in neurons some support axon guidance and synaptogenesis. That is because BACE not only catalyzes the first step in Aβ production-the cleavage of amyloid precursor protein-but also snips dozens of other substrates. Secretase experts had always advised low doses to avoid adverse events. What’s changed? For BACE inhibition itself, not much. Sperling, from Brigham and Women’s Hospital, Boston, co-chaired the session with Robert Vassar from Chicago's Northwestern University, who, with Martin Citron, had cloned BACE 24 years ago ( Vassar et al., 1999). Even Reisa Sperling, a self-professed skeptic of BACE inhibition, said she could envision a small trial. “BACE inhibition in primary prevention holds great potential,” said Paul Aisen, University of Southern California, San Diego, during a scientific session on the future of BACE inhibition. ![]()
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