ALS研究进展2015英文.pdf

R ev ie w s  K E Y N O T E R E V IE WDrug Discovery Today  Volume 00, Number 00  February 2016 REVIEWS Teaser A review of the current models, including animal models, used in ALS research and new models to accelerate drug discovery. A look into the future of ALS research Pascaline Clerc1, Scott Lipnick2 and Catherine Willett1 1 The Humane Society of the United States, 700 Professional Drive, Gaithersburg, MD 20879, USA 2Massachusetts General Hospital, Harvard Medical School, Department of Medicine, 55 Fruit Street, Boston, MA 02114, USA Although amyotrophic lateral sclerosis (ALS), also referred as ‘Lou Gehrig’s Disease,’ was first described in 1869 and the first disease-associated gene was discovered almost 20 years ago, the disease etiology is still not fully understood and treatment options are limited to one drug approved by the US Food and Drug Administration (FDA). The slow translational progress suggests that current research models are not ideal to study such a complicated disease and need to be re-examined. Progress will require greater insight into human genes and biology involved in ALS susceptibility, as well as a deeper understanding of disease phenotype at the histological and molecular levels. Improving human disease outcome will require directing focus toward improved assessment technologies and innovative approaches. Introduction Since the first gene associated with ALS was identified almost 20 years ago, researchers have relied primarily on animal models to study the mechanisms of disease progression and to identify therapies. These studies, funded mainly by the ALS Association and the National Institute of Health (/categorical_spending.aspx), have cost nearly US$700 million over the past 10 years in the USA alone. One of the main focuses has been on recapitulating the human disease in animal models, which has resulted in the identification of a single drug, riluzole, which was approved by the FDA for ALS treatment in 1995. However, the benefits