Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation

Amyotrophic lateral sclerosis (ALS) is a devastating disease caused by degeneration of motor neurons. As with all major neurodegenerative disorders, development of disease-modifying therapies has proven challenging for multiple reasons. Nevertheless, ALS is one of the few neurodegenerative diseases for which disease-modifying therapies are approved. Significant discoveries and advances have been made in ALS preclinical models, genetics, pathology, biomarkers, imaging and clinical readouts over the last 10-15 years. At the same time, novel therapeutic paradigms are being applied in areas of high unmet medical need, including neurodegenerative disorders. These developments have evolved our knowledge base, allowing identification of targeted candidate therapies for ALS with diverse mechanisms of action. In this Review, we discuss how this advanced knowledge, aligned with new approaches, can enable effective translation of therapeutic agents from preclinical studies through to clinical benefit for patients with ALS. We anticipate that this approach in ALS will also positively impact the field of drug discovery for neurodegenerative disorders more broadly.

Automated summary

Amyotrophic lateral sclerosis (ALS) is a devastating disease with degeneration of motor neurons. Despite the challenges, ALS has seen progress in the development of disease-modifying therapies. Significant advancements have been made in ALS research and novel therapeutic approaches are being applied to address unmet medical needs. This review discusses how advanced knowledge and new approaches can lead to effective translation of therapies for ALS and potentially impact drug discovery for neurodegenerative disorders.