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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| Format: | Article |
| Language: | English |
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De Gruyter
2017-01-01
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| Series: | Translational Neuroscience |
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| Online Access: | https://doi.org/10.1515/tnsci-2017-0001 |
| _version_ | 1818597393195597824 |
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| author | Ottesen Eric W. |
| author_facet | Ottesen Eric W. |
| author_sort | Ottesen Eric W. |
| collection | DOAJ |
| 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-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. |
| first_indexed | 2024-12-16T11:47:05Z |
| format | Article |
| id | doaj.art-86e1c44319ce480f8dbc8a4d5359f32e |
| institution | Directory Open Access Journal |
| issn | 2081-6936 |
| language | English |
| last_indexed | 2024-12-16T11:47:05Z |
| publishDate | 2017-01-01 |
| publisher | De Gruyter |
| record_format | Article |
| series | Translational Neuroscience |
| spelling | doaj.art-86e1c44319ce480f8dbc8a4d5359f32e2022-12-21T22:32:48ZengDe GruyterTranslational Neuroscience2081-69362017-01-01811610.1515/tnsci-2017-0001tnsci-2017-0001ISS-N1 makes the first FDA-approved drug for spinal muscular atrophyOttesen Eric W.0Department of Biomedical Sciences, Iowa State University, Ames, Iowa 50011, United States of AmericaSpinal 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.https://doi.org/10.1515/tnsci-2017-0001spinal muscular atrophyantisense oligonucleotidessurvival motor neuron proteinsmnspinrazaisis-smnrxionis-smnrxnusinerseniss-n1splicing regulation |
| spellingShingle | Ottesen Eric W. ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy Translational Neuroscience spinal muscular atrophy antisense oligonucleotides survival motor neuron protein smn spinraza isis-smnrx ionis-smnrx nusinersen iss-n1 splicing regulation |
| 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 | spinal muscular atrophy antisense oligonucleotides survival motor neuron protein smn spinraza isis-smnrx ionis-smnrx nusinersen iss-n1 splicing regulation |
| url | https://doi.org/10.1515/tnsci-2017-0001 |
| work_keys_str_mv | AT ottesenericw issn1makesthefirstfdaapproveddrugforspinalmuscularatrophy |