Improving clinical trial outcomes in amyotrophic lateral sclerosis

Nat Rev Neurol. 2021 Feb;17(2):104-118. doi: 10.1038/s41582-020-00434-z. Epub 2020 Dec 18.


Individuals who are diagnosed with amyotrophic lateral sclerosis (ALS) today face the same historically intransigent problem that has existed since the initial description of the disease in the 1860s - a lack of effective therapies. In part, the development of new treatments has been hampered by an imperfect understanding of the biological processes that trigger ALS and promote disease progression. Advances in our understanding of these biological processes, including the causative genetic mutations, and of the influence of environmental factors have deepened our appreciation of disease pathophysiology. The consequent identification of pathogenic targets means that the introduction of effective therapies is becoming a realistic prospect. Progress in precision medicine, including genetically targeted therapies, will undoubtedly change the natural history of ALS. The evolution of clinical trial designs combined with improved methods for patient stratification will facilitate the translation of novel therapies into the clinic. In addition, the refinement of emerging biomarkers of therapeutic benefits is critical to the streamlining of care for individuals. In this Review, we synthesize these developments in ALS and discuss the further developments and refinements needed to accelerate the introduction of effective therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / immunology*
  • Amyotrophic Lateral Sclerosis / therapy*
  • Clinical Trials as Topic / methods*
  • Disease Progression
  • Genetic Therapy / methods
  • Genetic Therapy / trends
  • Humans
  • Immunomodulating Agents / therapeutic use
  • Precision Medicine / methods
  • Precision Medicine / trends
  • Treatment Outcome


  • Immunomodulating Agents