title: Spinal muscular atrophy: an update on therapeutic progress.
abstract: Humans have two nearly identical copies of survival motor neuron gene: SMN1 and SMN2. Deletion or mutation of SMN1 combined with the inability of SMN2 to compensate for the loss of SMN1 results in spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. SMA affects 1 in ~6000 live births, a frequency much higher than in several genetic diseases. The major known defect of SMN2 is the predominant exon 7 skipping that leads to production of a truncated protein (SMNΔ7), which is unstable. Therefore, SMA has emerged as a model genetic disorder in which almost the entire disease population could be linked to the aberrant splicing of a single exon (i.e. SMN2 exon 7). Diverse treatment strategies aimed at improving the function of SMN2 have been envisioned. These strategies include, but are not limited to, manipulation of transcription, correction of aberrant splicing and stabilization of mRNA, SMN and SMNΔ7. This review summarizes up to date progress and promise of various in vivo studies reported for the treatment of SMA.
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, IA 50011, USA.
authors.forename: Joonbae
authors.initials: J
authors.lastname: Seo
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Howell
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Singh
authors.forename: Ravindra N
authors.initials: RN
authors.lastname: Singh
mesh_terms: D000818:Animals; D006801:Humans; D009134:Muscular Atrophy, Spinal / Q000628:therapy*
keywords: ALS; ASO; Antisense oligonucleotide; BBB; CREB; FDA; Food and Drug Administration; GSK-3; Genetic disease therapy; HDAC; ICV; IGF-1; IP; ISS-N1; ISS-N2; IV; JAK; Janus kinase; N-methyl d-aspartic acid; NMDA; NSAID; SAHA; SC; SMA; SMA therapeutics; SMN; STAT5; Spinal muscular atrophy; Splicing; Survival motor neuron; T-cell restricted intracellular antigen 1; TIA1; TSA; VPA; amyotrophic lateral sclerosis; antisense oligonucleotide; blood brain barrier; cyclic AMP response element binding protein; glycogen synthase kinase 3; heterogenous ribonucleoprotein A1; histone deacetylase; hnRNP A1; insulin-like growth factor 1; intracerebroventricular; intraperitoneal; intravascular; intronic splicing silencer N1; intronic splicing silencer N2; non-steroidal anti-inflammatory drug; scAAV; self-complimentary adeno-associated virus; signal transducer and activator of transcription 5; small nuclear ribonucleoprotein; snRNP; spinal muscular atrophy; subcutaneous; suberoylanilide hydroxamic acid; survival motor neuron; trichostatin A; valproic acid