Therapeutic advances in amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a progressive and rapidly fatal neurodegenerative disease in which both upper and lower motoneurones are involved. The recent discovery of mutations affecting the superoxide dismutase (SOD) gene has given impetus to research on the role of oxidative stress in the pathogenesis of familial ALS, while further evidence for a role of excitotoxicity in the disease process has arisen. In this review, Erik Louvel, Jacques Hugon and Adam Doble discuss these findings and, in addition, describe how a number of large, well-controlled clinical trials have taken place to test potential therapies suggested by different aetiological hypotheses, including immunosuppressive therapies, neurotrophic factors, antioxidants and anti-excitotoxic drugs. These trials have led to the first modest steps in the treatment of this devastating neurological disease.
Louvel
E
E
Rhöne-Poulenc Rorer Japan, Tokyo, Japan.
Hugon
J
J
Doble
A
A
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic / Q000639:trends; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals / Q000009:adverse effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D009154:Mutation / Q000235:genetics; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics*
D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D007166:Immunosuppressive Agents; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D013482:Superoxide Dismutase