afinersen

Afinersen (also known as ASO5 or ASO5-2) is an investigational antisense oligonucleotide (ASO) developed to treat amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) caused by hexanucleotide repeat expansions in the *C9orf72* gene. It is a mixed-backbone ASO designed to selectively suppress the expression of mutant *C9orf72* transcripts containing the G4C2 repeat expansion. By reducing these toxic transcripts, the therapy aims to decrease the accumulation of dipeptide repeat proteins and RNA foci, which are implicated in neuronal death. Afinersen was notably used in a single-patient expanded access protocol at UMass Chan Medical School to assess safety and biomarker response in a clinical setting.