Abstract

There is currently no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating disorder of the human nervous system that, due to motoneurone degeneration, causes progressive loss of muscle function and death. The relentless progression of ALS and the uniformly poor prognosis have been unhindered by a variety of therapeutic agents tested in previous clinical studies. Recently, two drugs, namely riluzole and recombinant human insulin-like growth factor-I (IGF-I), have been reported to benefit patients with ALS by improving survival or slowing disease progression. Several other drugs, such as gabapentin and various neurotrophic factors, are being investigated in on-going critical trials. Therapeutic developments in ALS have been hampered by the fact that the precise cause of the disease remains unknown. In addition, there are considerable variations in disease related characteristics among patients, rendering accurate measurements of disease progression difficult. Advances in theories of pathogenesis, such as genetic factors, glutamate excitotoxicity, oxidative stress, autoimmune mechanism and cytoskeletal abnormality will help guide the development of future therapies. Newer approaches to therapy may include suitable glutamate antagonists, small molecules that augment neurotrophic factor function, and anti-oxidants. Combination therapy of effective agents should be considered.

Original languageEnglish (US)
Pages (from-to)347-361
Number of pages15
JournalExpert Opinion on Investigational Drugs
Volume8
Issue number4
DOIs
StatePublished - Jan 1 1999

Keywords

  • Amyotrophic lateral sclerosis
  • Autoimmunity
  • Glutamate excitotoxicity
  • Insulin-like growth factor-1
  • Motoneurone neurodegeneration
  • Neurotrophic factors
  • Oxidative stress
  • Riluzole
  • Superoxide dismutase

ASJC Scopus subject areas

  • Pharmacology

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