[Gene-specific treatment approaches in amyotrophic lateral sclerosis in the present and future]

Area of Science:

• Neuroscience
• Genetics
• Pharmacology

Background:

• Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a monogenic component in up to 10% of cases.
• Mutations in genes like SOD1 and C9ORF72 are common, often leading to toxic gain-of-function mechanisms.
• Current therapeutic strategies are increasingly focusing on gene-specific approaches.

Purpose of the Study:

• To review gene-specific therapeutic developments for Amyotrophic Lateral Sclerosis (ALS).
• To discuss the potential and challenges of antisense oligonucleotide (ASO)-based and viral strategies.
• To highlight progress in treating both familial and sporadic forms of ALS.

Main Methods:

• Review of current gene-specific therapeutic developments for ALS.
• Focus on antisense oligonucleotide (ASO) and viral strategies.
• Discussion of pathomechanisms related to SOD1 and C9ORF72 mutations.

Main Results:

• Development of specific ASOs targeting SOD1 and C9ORF72 mRNAs for degradation.
• Promising interim results from clinical trials of these ASOs in ALS mouse models.
• Emerging gene-specific approaches for sporadic ALS compensating for pathomechanisms.

Conclusions:

• Gene-specific therapies, particularly ASOs, represent a promising treatment avenue for ALS.
• Targeting toxic gain-of-function mutations in SOD1 and C9ORF72 is a key strategy.
• Further research is needed to address pitfalls and challenges in the development of these advanced ALS treatments.