Therapeutic advances in 5q-linked spinal muscular atrophy

ABSTRACT Spinal muscular atrophy (SMA) is a severe and clinically-heterogeneous motor neuron disease caused, in most cases, by a homozygous mutation in the SMN1 gene. Regarding the age of onset and motor involvement, at least four distinct clinical phenotypes have been recognized. This clinical vari...

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Main Authors: Umbertina Conti Reed, Edmar Zanoteli
Format: Article
Language:English
Published: Thieme Revinter Publicações
Series:Arquivos de Neuro-Psiquiatria
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Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2018000400265&lng=en&tlng=en
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author Umbertina Conti Reed
Edmar Zanoteli
author_facet Umbertina Conti Reed
Edmar Zanoteli
author_sort Umbertina Conti Reed
collection DOAJ
description ABSTRACT Spinal muscular atrophy (SMA) is a severe and clinically-heterogeneous motor neuron disease caused, in most cases, by a homozygous mutation in the SMN1 gene. Regarding the age of onset and motor involvement, at least four distinct clinical phenotypes have been recognized. This clinical variability is, in part, related to the SMN2 copy number. By now, only supportive therapies have been available. However, promising specific therapies are currently being developed based on different mechanisms to increase the level of SMN protein; in particular, intrathecal antisense oligonucleotides that prevent the skipping of exon 7 during SMN2 transcription, and intravenous SMN1 insertion using viral vector. These therapeutic perspectives open a new era in the natural history of the disease. In this review, we intend to discuss the most recent and promising therapeutic strategies, with special consideration to the pathogenesis of the disease and the mechanisms of action of such therapies.
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publisher Thieme Revinter Publicações
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series Arquivos de Neuro-Psiquiatria
spelling doaj-art-43f8783e7c854a87b26f93e6c3be5e8d2025-08-20T02:05:50ZengThieme Revinter PublicaçõesArquivos de Neuro-Psiquiatria1678-422776426527210.1590/0004-282x20180011S0004-282X2018000400265Therapeutic advances in 5q-linked spinal muscular atrophyUmbertina Conti ReedEdmar ZanoteliABSTRACT Spinal muscular atrophy (SMA) is a severe and clinically-heterogeneous motor neuron disease caused, in most cases, by a homozygous mutation in the SMN1 gene. Regarding the age of onset and motor involvement, at least four distinct clinical phenotypes have been recognized. This clinical variability is, in part, related to the SMN2 copy number. By now, only supportive therapies have been available. However, promising specific therapies are currently being developed based on different mechanisms to increase the level of SMN protein; in particular, intrathecal antisense oligonucleotides that prevent the skipping of exon 7 during SMN2 transcription, and intravenous SMN1 insertion using viral vector. These therapeutic perspectives open a new era in the natural history of the disease. In this review, we intend to discuss the most recent and promising therapeutic strategies, with special consideration to the pathogenesis of the disease and the mechanisms of action of such therapies.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2018000400265&lng=en&tlng=enatrofia muscular espinhaldoença do neurônio motoroligonucleotídeos antissensoterapia genética
spellingShingle Umbertina Conti Reed
Edmar Zanoteli
Therapeutic advances in 5q-linked spinal muscular atrophy
Arquivos de Neuro-Psiquiatria
atrofia muscular espinhal
doença do neurônio motor
oligonucleotídeos antissenso
terapia genética
title Therapeutic advances in 5q-linked spinal muscular atrophy
title_full Therapeutic advances in 5q-linked spinal muscular atrophy
title_fullStr Therapeutic advances in 5q-linked spinal muscular atrophy
title_full_unstemmed Therapeutic advances in 5q-linked spinal muscular atrophy
title_short Therapeutic advances in 5q-linked spinal muscular atrophy
title_sort therapeutic advances in 5q linked spinal muscular atrophy
topic atrofia muscular espinhal
doença do neurônio motor
oligonucleotídeos antissenso
terapia genética
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2018000400265&lng=en&tlng=en
work_keys_str_mv AT umbertinacontireed therapeuticadvancesin5qlinkedspinalmuscularatrophy
AT edmarzanoteli therapeuticadvancesin5qlinkedspinalmuscularatrophy