Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a rapidly progressive fatal neurodegenerative disease affecting both upper and lower motor neurons. ALS clinical trials have historically had a high failure rate due to disease heterogeneity, rapid progression, and lack of validated biomarkers — but recent approvals of tofersen (for SOD1-ALS) and the conditional approval of AMX0035 (subsequently withdrawn from the EU) represent important steps forward. The discovery that 10–15% of ALS patients carry identifiable genetic mutations (SOD1, C9orf72, FUS, TDP-43) has enabled genotype-targeted trials.
Active trials investigate antisense oligonucleotides (ASOs) targeting SOD1, C9orf72, and FUS mutations; stem cell therapies (NurOwn); the HEALEY ALS Platform Trial (testing multiple agents simultaneously); brain-computer interfaces for communication; and biomarker studies using neurofilament light chain (NfL) to track disease activity and predict outcomes. Gene therapy approaches for SOD1-ALS are in early-phase development.
ALS trial eligibility typically requires confirmed ALS diagnosis per El Escorial criteria, symptom onset within 1–2 years, adequate respiratory function (FVC ≥60%), and in genetically targeted trials, confirmed mutation status.