The First Orally Deliverable Small Molecule for the Treatment of Spinal Muscular Atrophy.
| Autor: | Singh RN; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA., Ottesen EW; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA., Singh NN; Department of Biomedical Sciences, Iowa State University, Ames, IA, USA. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Neuroscience insights [Neurosci Insights] 2020 Nov 23; Vol. 15, pp. 2633105520973985. Date of Electronic Publication: 2020 Nov 23 (Print Publication: 2020). |
| DOI: | 10.1177/2633105520973985 |
| Abstrakt: | Spinal muscular atrophy (SMA) is 1 of the leading causes of infant mortality. SMA is mostly caused by low levels of Survival Motor Neuron (SMN) protein due to deletion of or mutation in the SMN1 gene. Its nearly identical copy, SMN2 , fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Correction of SMN2 exon 7 splicing by an antisense oligonucleotide (ASO), nusinersen (Spinraza™), that targets the intronic splicing silencer N1 (ISS-N1) became the first approved therapy for SMA. Restoration of SMN levels using gene therapy was the next. Very recently, an orally deliverable small molecule, risdiplam (Evrysdi™), became the third approved therapy for SMA. Here we discuss how these therapies are positioned to meet the needs of the broad phenotypic spectrum of SMA patients. Competing Interests: Declaration of conflicting interests:The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ISS-N1 target (US patent # 7,838,657) mentioned in this review was discovered in the Singh lab at UMASS Medical School (Worcester, MA, USA). Inventors, including NNS, RNS, and UMASS Medical School, are currently benefiting from licensing of ISS-N1 target to IONIS Pharmaceuticals/Biogen, which is marketing Spinraza™ (Nusinersen), the FDA-approved drug, based on ISS-N1 target. RNS is co-founder of RNACorrect, Inc., an Iowa-based small business engaged in research and development. (© The Author(s) 2020.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|