AMX0114

AMX0114 is an investigational antisense oligonucleotide (ASO) developed by Amylyx Pharmaceuticals for the treatment of amyotrophic lateral sclerosis (ALS). It is designed to target and inhibit calpain-2, a calcium-activated protease encoded by the CAPN2 gene. Calpain-2 has been identified as a critical effector of axonal degeneration, which is a key early contributor to ALS pathogenesis. By binding to CAPN2 mRNA, AMX0114 reduces calpain-2 protein levels, thereby aiming to protect motor neurons and slow disease progression. Preclinical studies have demonstrated that AMX0114 leads to potent, dose-dependent reductions in both CAPN2 mRNA and calpain-2 protein levels, improved neuronal survival—including in TDP-43 ALS models—and decreased neurofilament light chain (NfL), a biomarker of neuronal injury. The drug is currently being evaluated in the Phase 1 LUMINA trial via intrathecal administration[1][2][3][5][6].