Therapeutic developments in the treatment of amyotrophic lateral sclerosis

Mandy Jackson, Jerònia Lladó, Jeffrey D. Rothstein

Research output: Contribution to journalReview articlepeer-review

24 Scopus citations


Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterised by the selective death of motor neurons. The mechanisms and processes responsible for the selective loss of motor neurons are still unknown, however several hypotheses have been put forward, including oxidative damage and/or toxicity from intracellular aggregates due to mutant superoxide dismutase-1 activity, axonal strangulation from cytoskeletal abnormalities, loss of trophic factor support and glutamate-mediated excitotoxicity. These theories are based on a better understanding of the genetics of amyotrophic lateral sclerosis and on biochemical and pathological analysis of post-mortem tissue. They have led to the development of appropriate animal and cell culture models, allowing the sequence of events in motor neuronal degeneration to be unravelled and potential therapeutic agents to be screened. Unfortunately, the majority of therapeutics found to be efficacious in the animal and cell culture models have failed in human trials. Riluzole is still the only proven therapy in humans, shown to extend survival of amyotrophic lateral sclerosis patients by ∼ 3 months, but it has no effect on muscle strength. Other potential therapeutic approaches are being identified, including inhibition of caspase-mediated cell death, maintenance of mitochondrial integrity and energy production, regulation of glutamate homeostasis, reduction of inflammation and control of neurofilament synthesis. Hopefully, in the near future some new agents will be found that can alter the course of this devastating and fatal disease.

Original languageEnglish (US)
Pages (from-to)1343-1364
Number of pages22
JournalExpert Opinion on Investigational Drugs
Issue number10
StatePublished - Oct 1 2002


  • Amyotrophic lateral sclerosis
  • Antioxidants
  • Apoptosis
  • Excitotoxicity
  • Gene and stem cell therapy
  • Neurotrophic factors
  • Superoxide dismutrase-1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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