Investigating oral blarcamesine for treatment of early Alzheimer's disease.

Abstract

INTRODUCTION Alzheimer's disease (AD) is the most common neurodegenerative dementia affecting millions globally. Therapies primarily consist of symptomatic management and progression limitation. Further advances in treatments include disease-modifying therapies, many of which have unfavorable safety profiles and modest improvements in cognitive function. The need for novel disease-modifying therapies continues to grow as the burden of AD in the population increases. AREAS COVERED We outline approved disease-modifying therapies including the mechanisms of autophagy restoration through SIGMAR1 activation and its impact on neuronal homeostasis, and how oral blarcamesine, a SIGMAR1 agonist, demonstrates promise for early onset AD management. We then describe the Phase IIa and IIb/III clinical trials supporting the efficacy of blarcamesine in AD patients and other neurodegenerative diseases. Additionally, we discuss recent preclinical evidence supporting a preventive role for blarcamesine in AD. A Pubmed search was conducted for relevant literature regarding this topic using keywords including, but not limited to, 'blarcamesine,' 'disease-modifying therapy,' 'precision medicine,' 'sigma-1 receptor,' and 'SIGMAR1 agonist.' EXPERT OPINION Blarcamesine is a potential oral disease-modifying therapeutic candidate for early-stage AD that acts upstream of amyloid-beta pathogenesis and could prevent AD progression very early on, with emerging preclinical evidence also supporting its potential for disease prevention.