title: ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy.
abstract: Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children and infants. SMA is caused by deletions or mutations ofSurvival Motor Neuron 1(SMN1) gene.SMN2, a nearly identical copy ofSMN1, cannot compensate for the loss ofSMN1due to predominant skipping of exon 7. While various regulatory elements that modulateSMN2exon 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.
authors.affiliation: Department of Biomedical Sciences, Iowa State University, Ames, Iowa 50011, United States of America.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Ottesen
keywords: IONIS-SMNRX; ISIS-SMNRX; ISS-N1; SMN; Spinraza; antisense oligonucleotides; nusinersen; spinal muscular atrophy; splicing regulation; survival motor neuron protein