Amyotrophic lateral sclerosis (ALS) is a critical and incurable disease that affects the upper and lower motor neurons. Despite remarkable progress in understanding the pathological mechanisms of the disease, classical pharmacological clinical trials have failed to effectively cure ALS over the last twenty years. Recently, two different gene therapy approaches have been approved for SMA (Spinal muscular atrophy), a monogenic disease characterized by degeneration of lower motor neurons. This important breakthrough suggests that therapeutic solutions based on gene therapy could be effective for the treatment of ALS.
In this review published in January 2021, the authors, including clinicians and researchers from the Institute of Myology, take stock of trials on the disease and present:
- a summary of the possible reasons for the failure of traditional clinical trials in ALS,
- a focus on the emergence of gene therapy approaches for hereditary forms of ALS,
- the description of the clinical use of antisense oligonucleotides in three familial forms of ALS, due respectively to mutations in the SOD1, C9orf72 and FUS genes,
- preclinical and clinical studies based on AAV-mediated gene therapy approaches for both familial and sporadic cases of ALS.
The researchers thus highlight the potential of gene therapy as a transformative technology that will have a considerable impact on the treatment prospects of patients with ALS and on the design of future clinical trials.
