Another gene for ALS

Abstract

An important feature of amyotrophic lateral sclerosis (ALS), which is common to other major neurodegenerative diseases such as Alzheimer disease and Parkinson disease, is that the minority (5%–10%) of patients with an inherited form of ALS cannot be distinguished clinically from the majority who have no family history. This has encouraged the view that understanding the genetic, molecular, and cellular basis of familial ALS (fALS) will provide major insights into pathogenesis, and ultimately lead to the generation of effective therapies, for the much commoner sporadic form of disease. For more than a decade, the only gene clearly associated with fALS was SOD1 , which accounts for 20% of familial cases.1 The most significant development in ALS research since that initial breakthrough was the discovery that TDP-43 protein is both a constituent of ubiquitinated inclusions in ALS spinal cord motor neurons2 and also mutated in approximately 5% of patients with fALS.3 A smaller number of patients with ALS carry mutations in the gene for angiogenin4 but more than three-quarters of familial ALS cases have remained unexplained. It has long been clear that there are more ALS genes to be discovered. …