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ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy
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 var...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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De Gruyter Open
2017
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382937/ https://www.ncbi.nlm.nih.gov/pubmed/28400976 http://dx.doi.org/10.1515/tnsci-2017-0001 |
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author | Ottesen, Eric W. |
author_facet | Ottesen, Eric W. |
author_sort | Ottesen, Eric W. |
collection | PubMed |
description | 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-SMN(RX), ISIS-SMN(RX)), 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. |
format | Online Article Text |
id | pubmed-5382937 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | De Gruyter Open |
record_format | MEDLINE/PubMed |
spelling | pubmed-53829372017-07-20 ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy Ottesen, Eric W. Transl Neurosci Regular Articles 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-SMN(RX), ISIS-SMN(RX)), 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. De Gruyter Open 2017-01-26 /pmc/articles/PMC5382937/ /pubmed/28400976 http://dx.doi.org/10.1515/tnsci-2017-0001 Text en © 2017 Eric W. Ottesen http://creativecommons.org/licenses/by-nc-nd/3.0 This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. |
spellingShingle | Regular Articles Ottesen, Eric W. ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title | ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title_full | ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title_fullStr | ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title_full_unstemmed | ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title_short | ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy |
title_sort | iss-n1 makes the first fda-approved drug for spinal muscular atrophy |
topic | Regular Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5382937/ https://www.ncbi.nlm.nih.gov/pubmed/28400976 http://dx.doi.org/10.1515/tnsci-2017-0001 |
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