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Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I

Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting...

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Autores principales: Mirea, Andrada, Shelby, Elena-Silvia, Axente, Mihaela, Badina, Mihaela, Padure, Liliana, Leanca, Madalina, Dima, Vlad, Sporea, Corina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658131/
https://www.ncbi.nlm.nih.gov/pubmed/34884240
http://dx.doi.org/10.3390/jcm10235540
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author Mirea, Andrada
Shelby, Elena-Silvia
Axente, Mihaela
Badina, Mihaela
Padure, Liliana
Leanca, Madalina
Dima, Vlad
Sporea, Corina
author_facet Mirea, Andrada
Shelby, Elena-Silvia
Axente, Mihaela
Badina, Mihaela
Padure, Liliana
Leanca, Madalina
Dima, Vlad
Sporea, Corina
author_sort Mirea, Andrada
collection PubMed
description Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy.
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spelling pubmed-86581312021-12-10 Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I Mirea, Andrada Shelby, Elena-Silvia Axente, Mihaela Badina, Mihaela Padure, Liliana Leanca, Madalina Dima, Vlad Sporea, Corina J Clin Med Article Background: Spinal muscular atrophy (SMA) is a neuromuscular progressive disease, characterized by decreased amounts of survival motor neuron (SMN) protein, due to an autosomal recessive genetic defect. Despite recent research, there is still no cure. Nusinersen, an antisense oligonucleotide acting on the SMN2 gene, is intrathecally administered all life long, while onasemnogene abeparvovec-xioi, a gene therapy, is administered intravenously only once. Both therapies have proven efficacy, with best outcomes obtained when administered presymptomatically. In recent years, disease-modifying therapies such as nusinersen and onasemnogene abeparvovec-xioi have changed the natural history of SMA. Methods: We observed seven SMA type I patients, who received both therapies. We compared their motor function trajectories, ventilation hours and cough assist sessions to a control group of patients who received one therapy, in order to investigate whether combination therapy may be more effective than a single intervention alone. Results: Patients who received both therapies, compared to the monotherapy cohort, had the same motor function trajectory. Moreover, it was observed that the evolution of motor function was better in the 6 months following the first therapy than in the first 6 months after adding the second treatment. Conclusions: Our results suggest that early treatment is more important than combined therapy. MDPI 2021-11-26 /pmc/articles/PMC8658131/ /pubmed/34884240 http://dx.doi.org/10.3390/jcm10235540 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mirea, Andrada
Shelby, Elena-Silvia
Axente, Mihaela
Badina, Mihaela
Padure, Liliana
Leanca, Madalina
Dima, Vlad
Sporea, Corina
Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title_full Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title_fullStr Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title_full_unstemmed Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title_short Combination Therapy with Nusinersen and Onasemnogene Abeparvovec-xioi in Spinal Muscular Atrophy Type I
title_sort combination therapy with nusinersen and onasemnogene abeparvovec-xioi in spinal muscular atrophy type i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8658131/
https://www.ncbi.nlm.nih.gov/pubmed/34884240
http://dx.doi.org/10.3390/jcm10235540
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