Amyotrophic lateral sclerosis. Recent advances in pathogenesis and therapeutic trials

Abstract

We reviewed the current status of pathogenesis and therapeutic trials in amyotrophic lateral sclerosis (ALS). Clinical studies have identified several rare but definable causes for apparent ALS. Certain clinical features previously considered unlikely to occur in ALS are found on careful examination. Epidemiologic surveillance and recent studies of neurotoxic plant seeds used in Guam have shed light on the pathogenesis of endemic ALS. Extensive analyses of biochemical, metabolic, immunologic, viral, and toxic factors have provided provocative results requiring further studies. Reflecting on some of these hypotheses, therapeutic trials have been performed more vigorously than ever. Amyotrophic lateral sclerosis is now investigated at the molecular genetic level. Human autopsy and experimental animal studies have expanded our understanding of basic mechanisms involving motoneuronal degeneration. In the future, we must continue a relentless search for the pathogenesis of ALS, prospective clinical studies to define the limits of ALS, and well-designed, controlled therapeutic trials.