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Current Treatment Options in Neurology
Published in: Current Treatment Options in Neurology 3/2024

30-01-2024 | Amyotrophic Lateral Sclerosis

Translating the ALS Genetic Revolution into Therapies: A Review

Authors: Christine Meadows, MD, Naraharisetty Anita Rau, MD, Warda Faridi, MD, Cindy V. Ly, MD, PhD

Published in: Current Treatment Options in Neurology | Issue 3/2024

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Abstract

Purpose of Review

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease causing weakness, respiratory failure, and death within 3 to 5 years. Approximately, 10% of ALS cases have a genetic etiology (familial/fALS). The etiology of the remaining 90% of sporadic ALS (sALS) cases remains unknown. In this review, we provide an overview of approved and investigational therapies for fALS, as well as genetically informed therapeutic advances aimed at the larger sALS population.

Recent Findings

Antisense oligonucleotides (ASOs) are a promising strategy to treat toxic gain-of-function mutations underlying most forms of fALS. We discuss the recent approval of tofersen for ALS caused by mutation in SOD1. We also discuss progress in the development of therapies for fALS associated with C9orf72 hexanucleotide repeat expansions (C9orf72) and fused in sarcoma (FUS) mutations. Finally, we will discuss the rationale and status of molecular therapies for sALS targeting mediators of TDP-43 pathogenesis: ataxin-2 (ATXN2) and stathmin-2 (STMN2).

Summary

Advances in understanding the genetics of ALS have propelled the development of promising gene therapies. Lessons learned from tofersen continue to inform clinical trial design for a growing pipeline of therapies directed towards other fALS subtypes and sALS.
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Metadata
Title
Translating the ALS Genetic Revolution into Therapies: A Review
Authors
Christine Meadows, MD
Naraharisetty Anita Rau, MD
Warda Faridi, MD
Cindy V. Ly, MD, PhD
Publication date
30-01-2024
Publisher
Springer US
Published in
Current Treatment Options in Neurology / Issue 3/2024
Print ISSN: 1092-8480
Electronic ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-024-00781-y