title: Spinal muscular atrophy: a timely review.
abstract: Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by loss of motor neurons in the anterior horn of the spinal cord and resultant weakness. The most common form of SMA, accounting for 95% of cases, is autosomal recessive proximal SMA associated with mutations in the survival of motor neurons (SMN1) gene. Relentless progress during the past 15 years in the understanding of the molecular genetics and pathophysiology of SMA has resulted in a unique opportunity for rational, effective therapeutic trials. The goal of SMA therapy is to increase the expression levels of the SMN protein in the correct cells at the right time. With this target in sight, investigators can now effectively screen potential therapies in vitro, test them in accurate, reliable animal models, move promising agents forward to clinical trials, and accurately diagnose patients at an early or presymptomatic stage of disease. A major challenge for the SMA community will be to prioritize and develop the most promising therapies in an efficient, timely, and safe manner with the guidance of the appropriate regulatory agencies. This review will take a historical perspective to highlight important milestones on the road to developing effective therapies for SMA.
authors.affiliation: Department of Neurology, Ohio State University, Columbus, 43210, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kolb
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease / Q000266:history; D015316:Genetic Therapy / Q000266:history; D049672:History, 19th Century; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000266:history* / Q000628:therapy*; D009154:Mutation; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics / Q000266:history*
chemical_list: C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein