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

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.