Therapeutics: Microtubule-associated protein τ (tau; MAPT; FTDP-17); Rho-associated coiled-coil containing protein kinase 1 (ROCK1); ROCK2
Patient sample and fruit fly studies suggest ROCK1 or ROCK2 inhibitors could help treat PSP and corticobasal degeneration (CBD), which is caused by neuronal accumulation of a four-repeat isoform of tau. Levels of ROCK1, ROCK2 and insoluble tau were higher in postmortem cortical tissue samples from patients with PSP or CBD than in postmortem samples from healthy controls. In transgenic Drosophila expressing the four-repeat tau isoform, Eril fasudil - an inhibitor of the Drosophila homolog of ROCK1/ROCK2 - decreased expression of the tau isoform and its associated pathological phenotype in the eye compared with vehicle. Next steps could include testing ROCK inhibitors in mouse models of PSP and CBD.
Asahi Kasei Pharma Corp. and Eisai Co. Ltd. market the Rho kinase inhibitor Eril to prevent cerebral vasospasm after subarachnoid hemorrhage surgery and have the compound in Phase II testing to treat pulmonary arterial hypertension (PAH). ...