%0 Journal Article
%T ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy
%A Eric W. Ottesen
%J Archive of "Translational Neuroscience".
%D 2017
%R 10.1515/tnsci-2017-0001
%X 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
%K spinal muscular atrophy
%K antisense oligonucleotides
%K survival motor neuron protein
%K SMN
%K Spinraza
%K ISIS-SMNRX
%K IONIS-SMNRX
%K nusinersen
%K ISS-N1
%K splicing regulation
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382937/