In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy

Brain Sciences

KristineS. Ojala¹  StephenD. Meriney¹  ChristineJ. DiDonato²  EmilyJ. Reedich² 

[1] Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA;Human Molecular Genetics and Physiology Program, Stanley Manne Children’s Research Institute at Ann & Robert H. Lurie Children’s Hospital, Chicago, IL 60611, USA;

关键词: spinal muscular atrophy;    motoneuron disease;    neuromuscular disease;    therapeutics;   

DOI  :  10.3390/brainsci11020194

来源: DOAJ

【 摘 要 】

Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual’s quality of life, independence, and lifespan. SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. The recent advent and use of genetically targeted therapies have transformed SMA into a prototype for monogenic disease treatment in the era of genetic medicine. Many SMA-affected individuals receiving these therapies achieve traditionally unobtainable motor milestones and survival rates as medicines drastically alter the natural progression of this disease. This review discusses historical SMA progression and underlying disease mechanisms, highlights advances made in therapeutic research, clinical trials, and FDA-approved medicines, and discusses possible second-generation and complementary medicines as well as optimal temporal intervention windows in order to optimize motor function and improve quality of life for all SMA-affected individuals.

【 授权许可】

Unknown