The sense of antisense therapies in ALS

Trends Mol Med. 2024 Mar;30(3):252-262. doi: 10.1016/j.molmed.2023.12.003. Epub 2024 Jan 11.

Abstract

Treatment of patients with amyotrophic lateral sclerosis (ALS) has entered a new era now that encouraging results about antisense oligonucleotides (ASOs) are becoming available and a first ASO therapy for ALS has been approved by the FDA. Moreover, there is hope not only that ALS can be stopped but also that symptoms can be reversed. Until now, degrading ASOs seemed to be successful mostly for rarer forms of familial ALS. However, the first attempts to correct mis-splicing events in sporadic ALS are underway, as well as a clinical trial examining interference with a genetic modifier. In this review, we discuss the current status of using ASOs in ALS and the possibilities and pitfalls of this therapeutic strategy.

Keywords: TDP-43; amyotrophic lateral sclerosis; antisense oligos; motor neuron; neurodegeneration.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis* / drug therapy
  • Amyotrophic Lateral Sclerosis* / therapy
  • Humans
  • Oligonucleotides, Antisense / therapeutic use
  • RNA Splicing

Substances

  • Oligonucleotides, Antisense

Supplementary concepts

  • Amyotrophic lateral sclerosis 1