Spinal muscular atrophy.
Spinal muscular atrophy is an autosomal recessive neurodegenerative disease characterised by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalised weakness. It is caused by homozygous disruption of the survival motor neuron 1 (SMN1) gene by deletion, conversion, or mutation. Although no medical treatment is available, investigations have elucidated possible mechanisms underlying the molecular pathogenesis of the disease. Treatment strategies have been developed to use the unique genomic structure of the SMN1 gene region. Several candidate treatment agents have been identified and are in various stages of development. These and other advances in medical technology have changed the standard of care for patients with spinal muscular atrophy. In this Seminar, we provide a comprehensive review that integrates clinical manifestations, molecular pathogenesis, diagnostic strategy, therapeutic development, and evidence from clinical trials.
Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Mitchell R
MR
Lunn
Ching H
CH
Wang
D000200:Action Potentials; D000588:Amines / Q000627:therapeutic use; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics*; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004576:Electromyography; D000077206:Gabapentin; D015723:Gene Library; D006801:Humans; D008967:Molecular Biology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010654:Phenylbutyrates / Q000627:therapeutic use; D016601:RNA-Binding Proteins / Q000235:genetics*; D016032:Randomized Controlled Trials as Topic; D055532:SMN Complex Proteins; D012720:Severity of Illness Index; D014897:Spinal Muscular Atrophies of Childhood / Q000145:classification / Q000235:genetics / Q000503:physiopathology; D055533:Survival of Motor Neuron 1 Protein; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
D000588:Amines; D017362:Cyclic AMP Response Element-Binding Protein; D003509:Cyclohexanecarboxylic Acids; D009419:Nerve Tissue Proteins; D010654:Phenylbutyrates; D016601:RNA-Binding Proteins; D055532:SMN Complex Proteins; C526471:SMN1 protein, human; D055533:Survival of Motor Neuron 1 Protein; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin