The clinical trial landscape in amyotrophic lateral sclerosis—Past, present, and future

• Published in: Medicinal research reviews Vol. 40; no. 4; pp. 1352 - 1384
• Main Authors: Wobst, Heike J., Mack, Korrie L., Brown, Dean G., Brandon, Nicholas J., Shorter, James
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.07.2020
• Subjects: ALS preclinical strategies; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - therapy; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Autophagy - drug effects; Clinical trials; Clinical Trials as Topic; Drug Approval; edaravone; Humans; Immunologic Factors - chemistry; Immunologic Factors - pharmacology; Immunologic Factors - therapeutic use; riluzole; edaravone; clinical trials; ALS preclinical strategies; amyotrophic lateral sclerosis; riluzole
• ISSN: 0198-6325; 1098-1128; 1098-1128
• DOI: 10.1002/med.21661

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive loss of muscle function. It is the most common adult‐onset form of motor neuron disease, affecting about 16 000 people in the United States alone. The average survival is about 3 years. Only two interventional drugs, the antiglutamatergic small‐molecule riluzole and the more recent antioxidant edaravone, have been approved for the treatment of ALS to date. Therapeutic strategies under investigation in clinical trials cover a range of different modalities and targets, and more than 70 different drugs have been tested in the clinic to date. Here, we summarize and classify interventional therapeutic strategies based on their molecular targets and phenotypic effects. We also discuss possible reasons for the failure of clinical trials in ALS and highlight emerging preclinical strategies that could provide a breakthrough in the battle against this relentless disease.