title: Perspectives on clinical trials in spinal muscular atrophy.
abstract: Spinal muscular atrophy is one of the most heterogeneous of the single-gene neuromuscular disorders. The broad spectrum of severity, with onset from the prenatal period to adulthood, presents unique challenges in the design and implementation of clinical trials. The clinical classification of subjects into severe (type 1), intermediate (type 2), and mild (type 3) subtypes has proved useful both in enhancing communication among clinicians internationally and in forging the collaborative development of outcome measures for clinical trials. Ideally, clinical trial design in spinal muscular atrophy must take into account the spinal muscular atrophy type, patient age, severity-of-affection status, nature of the therapeutic approach, timing of the proposed intervention relative to disease progression, and relative homogeneity of the cohort to be studied. Following is an overview of the challenges and opportunities, current and future therapeutic strategies, and progress to date in clinical trials in spinal muscular atrophy.
authors.affiliation: Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. swoboda@genetics.utah.edu
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
authors.forename: John T
authors.initials: JT
authors.lastname: Kissel
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Crawford
authors.forename: Mark B
authors.initials: MB
authors.lastname: Bromberg
authors.forename: Gyula
authors.initials: G
authors.lastname: Acsadi
authors.forename: Guy
authors.initials: G
authors.lastname: D'Anjou
authors.forename: Kristin J
authors.initials: KJ
authors.lastname: Krosschell
authors.forename: Sandra P
authors.initials: SP
authors.lastname: Reyna
authors.forename: Mary K
authors.initials: MK
authors.lastname: Schroth
authors.forename: Charles B
authors.initials: CB
authors.lastname: Scott
authors.forename: Louise R
authors.initials: LR
authors.lastname: Simard
mesh_terms: D002648:Child; D002986:Clinical Trials as Topic / Q000592:standards / Q000639:trends; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical / Q000639:trends; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D055532:SMN Complex Proteins; D014897:Spinal Muscular Atrophies of Childhood / Q000145:classification / Q000235:genetics* / Q000628:therapy*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins