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In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy

Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive para...

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Autores principales: Ojala, Kristine S., Reedich, Emily J., DiDonato, Christine J., Meriney, Stephen D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915832/
https://www.ncbi.nlm.nih.gov/pubmed/33562482
http://dx.doi.org/10.3390/brainsci11020194
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author Ojala, Kristine S.
Reedich, Emily J.
DiDonato, Christine J.
Meriney, Stephen D.
author_facet Ojala, Kristine S.
Reedich, Emily J.
DiDonato, Christine J.
Meriney, Stephen D.
author_sort Ojala, Kristine S.
collection PubMed
description Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual’s quality of life, independence, and lifespan. SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. The recent advent and use of genetically targeted therapies have transformed SMA into a prototype for monogenic disease treatment in the era of genetic medicine. Many SMA-affected individuals receiving these therapies achieve traditionally unobtainable motor milestones and survival rates as medicines drastically alter the natural progression of this disease. This review discusses historical SMA progression and underlying disease mechanisms, highlights advances made in therapeutic research, clinical trials, and FDA-approved medicines, and discusses possible second-generation and complementary medicines as well as optimal temporal intervention windows in order to optimize motor function and improve quality of life for all SMA-affected individuals.
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spelling pubmed-79158322021-03-01 In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy Ojala, Kristine S. Reedich, Emily J. DiDonato, Christine J. Meriney, Stephen D. Brain Sci Review Until the recent development of disease-modifying therapeutics, spinal muscular atrophy (SMA) was considered a devastating neuromuscular disease with a poor prognosis for most affected individuals. Symptoms generally present during early childhood and manifest as muscle weakness and progressive paralysis, severely compromising the affected individual’s quality of life, independence, and lifespan. SMA is most commonly caused by the inheritance of homozygously deleted SMN1 alleles with retention of one or more copies of a paralog gene, SMN2, which inversely correlates with disease severity. The recent advent and use of genetically targeted therapies have transformed SMA into a prototype for monogenic disease treatment in the era of genetic medicine. Many SMA-affected individuals receiving these therapies achieve traditionally unobtainable motor milestones and survival rates as medicines drastically alter the natural progression of this disease. This review discusses historical SMA progression and underlying disease mechanisms, highlights advances made in therapeutic research, clinical trials, and FDA-approved medicines, and discusses possible second-generation and complementary medicines as well as optimal temporal intervention windows in order to optimize motor function and improve quality of life for all SMA-affected individuals. MDPI 2021-02-05 /pmc/articles/PMC7915832/ /pubmed/33562482 http://dx.doi.org/10.3390/brainsci11020194 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ojala, Kristine S.
Reedich, Emily J.
DiDonato, Christine J.
Meriney, Stephen D.
In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title_full In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title_fullStr In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title_full_unstemmed In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title_short In Search of a Cure: The Development of Therapeutics to Alter the Progression of Spinal Muscular Atrophy
title_sort in search of a cure: the development of therapeutics to alter the progression of spinal muscular atrophy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915832/
https://www.ncbi.nlm.nih.gov/pubmed/33562482
http://dx.doi.org/10.3390/brainsci11020194
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