Alzheimer’s disease and the clinical stage sigma-1 agonist blarcamesine
The sigma-1 receptor was initially mistaken for an opioid receptor but was later identified as a chaperone protein that regulates cellular stress and calcium balance, playing a role in neurodegenerative diseases. Blarcamesine is an oral drug that targets the sigma-1 and muscarinic receptors to restore brain cell function, reduce harmful protein buildup, and promote waste clearance, which may help slow disease progression. In a Phase 2b/3 trial for early Alzheimer’s disease, blarcamesine significantly improved cognitive decline on the ADAS-Cog13 scale and reduced brain volume loss but did not achieve statistical significance on a key functional measure. The ongoing ATTENTION-AD trial is evaluating its long-term effects, with early findings suggesting that starting treatment sooner leads to better cognitive and functional outcomes.