Therapeutic tools for familial ALS

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Familial Amyotrophic Lateral Sclerosis (FALS) constitutes 10-15% of ALS cases, with identified causal genes in over 70% of patients.
• Animal models exist for FALS, primarily for frequently mutated genes, aiding therapeutic development.

Purpose of the Study:

• To review the current landscape of experimental treatments for FALS.
• To highlight promising therapeutic strategies and ongoing clinical trials for FALS patients.

Main Methods:

• Gene-specific therapies, including antisense oligonucleotides (ASO) delivered via viral vectors (AAV) targeting SOD1 mutations.
• Antibody-based therapies targeting misfolded SOD1 protein.
• Microbiota modulation as a therapeutic strategy, particularly for C9ORF72 models.

Main Results:

• Gene-specific therapies, especially AAV9+anti-SOD1 ASO, have shown significant success in preventing or halting disease progression in animal models.
• Antibody-based therapies are effective but less so than gene therapies, with epitope selection being a key challenge.
• Microbiota modulation presents a safe and easily administered approach with promising results in C9ORF72 models.

Conclusions:

• The field of experimental FALS treatment is rapidly advancing with promising results.
• Several therapeutic strategies, including gene-specific and microbiota-based approaches, are under investigation in ongoing human clinical trials.
• There is a significant unmet need for effective FALS treatments, driving innovation and research.