Amyotrophic lateral sclerosis: current and future treatment strategies.
Amyotrophic lateral sclerosis (ALS) is a fatal, enigmatic disorder characterised by relentless progression of muscle wasting and weakness until death ensues due to respiratory muscle failure. Intellectual functions are usually spared. ALS, known also as motor neuron disease (MND) in the UK, maladie de Charcot in France and Lou Gehrig's disease in the US, is usually sporadic, but between 5 and 10% of all cases are hereditary, usually inherited as autosomal dominant. Previously thought to be untreatable, as well as incurable, just in the last 3 years ALS has been the greatest clinical application of recent exciting break-throughs in preclinical neurobiology research. Although definitive information regarding the cause(s) and pathogenesis of ALS still escapes us, meaningful demonstration of intercession in the downhill course with specific therapy has been suggested, giving reason to be hopeful, if cautiously and critically optimistic. This review focuses on the recent work from the fields of growth/trophic factors, glutamate/neurotoxicity, neuroprotection and proteases and inhibitors, as well as the approaches to measuring specific effects in patients with the illness. It ends with a eye to the horizon, and the future, and where ALS treatment strategies may be heading after the millennium.
Festoff
B W
BW
Neurobiology Research Laboratory, Veterans Affairs Medical Center, Kansas City, Missouri, USA.
D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D017209:Apoptosis / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor; D002986:Clinical Trials as Topic; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000627:therapeutic use; D019782:Riluzole; D013844:Thiazoles / Q000627:therapeutic use
D020934:Ciliary Neurotrophic Factor; D009419:Nerve Tissue Proteins; D013844:Thiazoles; D007334:Insulin-Like Growth Factor I; D019782:Riluzole