Campus Units
Biomedical Sciences
Document Type
Article
Publication Version
Published Version
Publication Date
1-2017
Journal or Book Title
Translational Neuroscience
Volume
8
Issue
1
First Page
1
Last Page
6
DOI
10.1515/tnsci-2017-0001
Abstract
Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. SMN2, a nearly identical copy of SMN1, cannot compensate for the loss of SMN1 due to predominant skipping of exon 7. While various regulatory elements that modulate SMN2 exon 7 splicing have been proposed, intronic splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far for antisense oligonucleotide-mediated splicing correction in SMA. Upon procuring exclusive license from the University of Massachussets Medical School in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical development of Spinraza™ (synonyms: Nusinersen, IONIS-SMNRX, ISIS-SMNRX), an antisense drug based on ISS-N1 target. Spinraza™ showed very promising results at all steps of the clinical development and was approved by US Food and Drug Administration (FDA) on December 23, 2016. Spinraza™ is the first FDA-approved treatment for SMA and the first antisense drug to restore expression of a fully functional protein via splicing correction. The success of Spinraza™ underscores the potential of intronic sequences as promising therapeutic targets and sets the stage for further improvement of antisense drugs based on advanced oligonucleotide chemistries and delivery protocols.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Copyright Owner
The Author
Copyright Date
2017
Language
en
File Format
application/pdf
Recommended Citation
Ottesen, Eric W., "ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy" (2017). Biomedical Sciences Publications. 35.
https://lib.dr.iastate.edu/bms_pubs/35
Included in
Medical Biotechnology Commons, Medical Genetics Commons, Nervous System Diseases Commons, Pharmacy and Pharmaceutical Sciences Commons
Comments
This article is published as Ottesen, Eric W. "ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy." Translational Neuroscience 8, no. 1 (2017): 1-6, doi: 10.1515/tnsci-2017-0001. Posted with permission.