BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Muscarinic acetylcholine receptor M1 (CHRM1; HM1); glial fibrillary acidic protein (GFAP)

February 18, 2016 8:00 AM UTC

Patient sample, fly and mouse studies suggest inhibiting CHRM1 could help treat Alexander disease, which is caused by GFAP mutations that result in impaired glial cell function. In postmortem patient brain tissue, CHRM1 levels were higher than in normal controls. Screening of a compound library in a transgenic GFAP-mutant Drosophila model of Alexander disease identified the CHRM1 inhibitor Cuvposa glycopyrrolate as a potent inhibitor of apoptotic activity in glial cells. In the model, the compound decreased the number of flies that had seizures compared with vehicle. Also in the model, two CHRM1 inhibitor tool compounds decreased apoptotic activity in glial cells. Next steps could include testing Cuvposa and other CHRM1 inhibitors in mammalian models of Alexander disease...