Understanding the Causes of Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a human disease resulting from the degeneration of motor neurons in the brain, spinal cord, and peripheral nervous system. The resultant clinical features include weakness of the arms, legs, and face and difficulties with speech, swallowing, and breathing. ALS affects women and men, regardless of ancestry, and the risk of disease increases with age. Its clinical progression is one of the fastest of the neurodegenerative diseases, with death (often from respiratory failure) typically occurring within 3 to 5 years after onset. The incidence is approximately 2 per 100,000 persons per year, and the prevalence is approximately 6 per 100,000 persons.¹

(...) In this issue of the Journal, Dunckley et al.⁸ describe a genomewide association study of patients with ALS. The associations found in the first-pass analysis were confirmed in two additional series; 10 genetic loci were significantly associated with ALS in all three populations. The most significant association was for a SNP near an uncharacterized gene on chromosome 1. Since the function and relevance of this gene in ALS is not known, the authors showed that the protein it encodes was expressed in spinal cord and non–neural tissue specimens from unaffected persons, as well as in spinal-cord specimens from patients with ALS. Perhaps this pathway, if validated in other studies, could lead to a new approach to treatment of ALS.