One of the things that looked really bad in the original data about aducanumab (aduhelm) is the complete lack of association between the reduction in Ab and clinical benefit, as shown here:
A lot to learn from the new Sanofi abstract for @movedisorder 2021 meeting, on their compound (venglustat, a glucosylceramide synthase inhibitor) aimed to treat people with Parkinson's disease and GBA mutations. A short 🧵.
First, some background: In preclinical mouse models, one with GBA mutations and one with a SNCA mutation, the compound worked great! In both it reduced levels of glycosphignolipids, reduced levels of a-synuclein and improved phenotypes related to cognition.
Mar 24, 2021 • 13 tweets • 4 min read
It is time for a 🧵 about the Venglustat trial by Sanofi, targeting PD with GBA mutations.
Many of the things I am saying here, I have already said before, for example at the @movedisorder 2019 meeting in Nice, in different talks and here as well.
fiercebiotech.com/biotech/sanofi…
The approach behind Venglustat was based on the (likely incorrect) notion that the problem with GBA mutations in PD is accumulation of glucosylceramide, one of the substrates of GBA. Venglustat can penetrate the brain reduce glucosylceramide levels. fabrydiseasenews.com/venglustat-ibi…
