Challenges and opportunities in clinical trials for spinal muscular atrophy.
Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.
Hirtz
D
D
National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA. hirtzd@ninds.nih.gov
Iannaccone
S
S
Heemskerk
J
J
Gwinn-Hardy
K
K
Moxley
R
R
Rowland
L P
LP
D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols / Q000592:standards*; D002986:Clinical Trials as Topic / Q000592:standards; D017362:Cyclic AMP Response Element-Binding Protein / Q000819:agonists / Q000378:metabolism; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007391:International Cooperation; D009046:Motor Neurons / Q000378:metabolism; D015337:Multicenter Studies as Topic / Q000592:standards; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000503:physiopathology / Q000628:therapy*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000819:agonists / Q000378:metabolism; D012042:Registries / Q000592:standards; D055532:SMN Complex Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins