Risk Factors and Emerging Therapies in Amyotrophic Lateral Sclerosis

Int J Mol Sci. 2019 May 28;20(11):2616. doi: 10.3390/ijms20112616.

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by a permanent degeneration of both upper and lower motor neurons. Many different genes and pathophysiological processes contribute to this disease, however its exact cause remains unclear. Therefore, it is necessary to understand this heterogeneity to find effective treatments. In this review, we focus on selected environmental and genetic risk factors predisposing to ALS and highlight emerging treatments in ALS therapy. Of numerous defective genes associated with ALS, we focus on four principal genes that have been identified as definite causes of ALS: the SOD1 gene, C9orf72, TDP-43, as well as the recently identified TBK1. We also provide up-to-date information on selected environmental factors that have historically been considered as key players in ALS development and pathogenesis. In parallel to our survey of known risk factors, we also discuss emerging ALS stem cell therapies and experimental medicines currently undergoing phase II and III clinical trials.

Keywords: ALS; ALS treatment; environmental factors; genetic factors; risk factors.

Publication types

  • Review

MeSH terms

  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Amyotrophic Lateral Sclerosis / therapy
  • Animals
  • C9orf72 Protein / genetics
  • C9orf72 Protein / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genetic Predisposition to Disease*
  • Genetic Therapy
  • Humans
  • Molecular Targeted Therapy
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism

Substances

  • C9orf72 Protein
  • C9orf72 protein, human
  • DNA-Binding Proteins
  • SOD1 protein, human
  • TARDBP protein, human
  • Superoxide Dismutase-1