Gene therapy for ALS: A review.

Area of Science:

• Neuroscience
• Genetics
• Biotechnology

Background:

• Amyotrophic lateral sclerosis (ALS) presents significant challenges for gene therapy due to limited targets and difficulties in accessing the central nervous system (CNS).
• Recent breakthroughs in understanding ALS pathogenesis and genetics, alongside advancements in CNS targeting and gene delivery technologies, are creating new therapeutic avenues.

Purpose of the Study:

• To provide a comprehensive review of current gene therapy strategies for amyotrophic lateral sclerosis (ALS).
• To explore the application of various gene-based approaches across different genetic subtypes and sporadic ALS.
• To assess the progress of preclinical and clinical trials for gene therapy in ALS.

Main Methods:

• Review of antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR gene editing, adeno-associated virus (AAV)-mediated gene delivery, and antibody-based therapies.
• Analysis of preclinical studies and ongoing/completed human clinical trials for ALS gene therapy.
• Examination of therapeutic implementations for specific genetic mutations (SOD1, C9orf72, ATXN2, FUS) and sporadic ALS.

Main Results:

• Multiple gene therapy approaches are being investigated and tested in clinical trials for various forms of ALS.
• Significant progress has been made in developing techniques for CNS targeting, gene delivery, and gene editing relevant to ALS.
• The reviewed methods show promise for addressing both genetically defined and sporadic ALS cases.

Conclusions:

• Gene therapy holds transformative potential for treating amyotrophic lateral sclerosis (ALS).
• Ongoing research and clinical trials are advancing the field toward developing true disease-modifying treatments for ALS.
• The integration of genetic insights with advanced gene therapy technologies offers a promising future for ALS patients.