molecules of the month

Context. Neflamapimod (EIP Pharma, VX-745) is an oral, brain-penetrant p38α kinase inhibitor under development for neurodegenerative disorders. Among the roles of p38α MAPK is the activation of Rab5, a small endosome-associated Ras GTPase that regulates intracellular trafficking pathways. This, coupled with the involvement of Rab5 in the molecular mechanisms leading to the degeneration of basal forebrain cholinergic neurons (BFCNs), led to the hypothesis that inhibiting p38α could be a therapeutic strategy for diseases associated with BFCN dysfunction, such as dementia with Lewy bodies (DLB). Supported by mouse data, neflamapimod, likely the most advanced p38α MAPK inhibitor, has since progressed to clinical development, and two Ph. II studies have been completed (NCT03402659 and NCT04001517). Although data from the REVERSE-SD study in…