Gene Therapy in Amyotrophic Lateral Sclerosis

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Over 50 genes are linked to ALS and ALS/frontotemporal dementia (FTD) spectrum diseases, with C9orf72, SOD1, TARDBP, and FUS mutations being the most prevalent.
• Decades of research have focused on understanding the pathogenic mechanisms of these genetic mutations in ALS/FTD.

Purpose of the Study:

• To provide an overview of gene therapy advancements for ALS/FTD.
• To focus on therapeutic strategies targeting the most common genetic mutations: C9orf72, SOD1, TARDBP, and FUS.

Main Methods:

• Review of gene therapy strategies including RNA inhibition (microRNA, ASOs), RNA interference (RNAi), mutant protein inhibition (antibodies), and genome editing (CRISPR/Cas).
• Analysis of the application of these strategies in preclinical studies and clinical trials for ALS/FTD.

Main Results:

• Gene therapy approaches show promise in suppressing toxic gene products associated with ALS/FTD.
• Several gene therapy strategies, particularly for C9orf72 and SOD1 mutations, have progressed to clinical trials.

Conclusions:

• Gene therapy offers a promising avenue for treating ALS/FTD by directly addressing the underlying genetic causes.
• Continued research and clinical application of these gene-targeting strategies are crucial for developing effective ALS/FTD treatments.