Silence superoxide dismutase 1 (SOD1): a promising therapeutic target for amyotrophic lateral sclerosis (ALS)

Research output: Contribution to journalReview article

Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disorder that targets upper and lower motor neurons and leads to fatal muscle paralysis. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for 15% of familial ALS cases, but several studies have indicated that SOD1 dysfunction may also play a pathogenic role in sporadic ALS. SOD1 induces numerous toxic effects through the pathological misfolding and aggregation of mutant SOD1 species, hence a reduction of the levels of toxic variants appears to be a promising therapeutic strategy for SOD1-related ALS. Several methods are used to modulate gene expression in vivo; these include RNA interference, antisense oligonucleotides (ASOs) and CRISPR/Cas9 technology. Areas covered: This paper examines the current approaches for gene silencing and the progress made in silencing SOD1 in vivo. It progresses to shed light on the key results and pitfalls of these studies and highlights the future challenges and new perspectives for this exciting research field. Expert opinion: Gene silencing strategies targeting SOD1 may represent effective approaches for familial and sporadic ALS-related neurodegeneration; however, the risk of off-target effects must be minimized, and effective and minimally invasive delivery strategies should be fine-tuned.

Original languageEnglish
Pages (from-to)295-310
Number of pages16
JournalExpert Opinion on Therapeutic Targets
Volume24
Issue number4
DOIs
Publication statusPublished - Apr 2 2020

Keywords

  • ALS
  • Amyotrophic lateral sclerosis
  • antisense oligonucleotides
  • Cas9
  • CRISPR
  • gene silencing
  • RNA interference
  • SOD1
  • superoxide dismutase 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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