The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer’s disease patients
The discovery of BACE1 inhibitors that reduce β-amyloid peptides in Alzheimer’s disease (AD) patients has been an encouraging development in the quest for a disease-modifying therapy. Kennedy and colleagues now report the discovery of verubecestat, a structurally unique, orally bioavailable small molecule that potently inhibits brain BACE1 activity resulting in a reduction in Aβ peptides in the cerebrospinal fluid of animals, healthy volunteers, and AD patients. No dose-limiting toxicities were observed in chronic animal toxicology studies or in phase 1 human studies, thus reducing safety concerns raised by previous reports of BACE inhibitors and BACE1 knockout mice.
According
to the World Health Organization over 36 million people world-wide are affected by dementia, of which the majority have
Alzheimer’s. This number is forecast to double by 2030 and triple by 2050 if no
treatment is discovered. So great hopes are placed on verubecestat.
