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Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease

BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range...

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Autores principales: Rao, Vamshi K., Kapp, Daniel, Schroth, Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Academy of Managed Care Pharmacy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408414/
https://www.ncbi.nlm.nih.gov/pubmed/30582825
http://dx.doi.org/10.18553/jmcp.2018.24.12-a.s3
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author Rao, Vamshi K.
Kapp, Daniel
Schroth, Mary
author_facet Rao, Vamshi K.
Kapp, Daniel
Schroth, Mary
author_sort Rao, Vamshi K.
collection PubMed
description BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range of phenotype expression resulting in variable age of symptom onset, maximum motor strength achieved, and survival. Without intervention, infants with a more severe form of the disease (type 1 SMA) die before 2 years of age. Although it is rare, SMA is the most common fatal inherited disease of infancy, and until recently, treatment was primarily supportive. In 2016, a new agent, nusinersen, was approved by the FDA. Other treatments are in development, including a gene therapy, AVXS-101. These treatments are not only improving the lives of patients with SMA and their families, they are changing the disease phenotype. They have the greatest benefit when given early in the disease course. OBJECTIVES: To discuss current knowledge about SMA, provide clinical evidence for available and emerging treatment options, and present approaches for adding new therapies to hospital/health system formularies to ensure timely access to newly approved therapies for SMA. SUMMARY: Advances in clinical care have significantly extended the lives of individuals with SMA, and research into the genetic mechanisms leading to disease have revealed strategies for intervention that target the underlying cause of SMA. Nusinersen is now on the market, and other treatment options, such as AVXS-101, may soon be approved. This article provides an overview of SMA and the genetic mechanisms leading to SMN deficiency, then describes how new and emerging treatments work to overcome this deficiency and prevent associated nerve damage and disability. In addition, we discuss steps for incorporating AVXS-101 into hospital/health system formularies, along with barriers and concerns that may delay access, based in part on lessons learned with nusinersen.
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spelling pubmed-104084142023-08-09 Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease Rao, Vamshi K. Kapp, Daniel Schroth, Mary J Manag Care Spec Pharm Supplement BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease that, in most cases, involves homozygous deletion of the SMN1 gene. This causes a deficiency in survival motor neuron (SMN) protein, which plays a critical role in motor neuron development. SMA has a range of phenotype expression resulting in variable age of symptom onset, maximum motor strength achieved, and survival. Without intervention, infants with a more severe form of the disease (type 1 SMA) die before 2 years of age. Although it is rare, SMA is the most common fatal inherited disease of infancy, and until recently, treatment was primarily supportive. In 2016, a new agent, nusinersen, was approved by the FDA. Other treatments are in development, including a gene therapy, AVXS-101. These treatments are not only improving the lives of patients with SMA and their families, they are changing the disease phenotype. They have the greatest benefit when given early in the disease course. OBJECTIVES: To discuss current knowledge about SMA, provide clinical evidence for available and emerging treatment options, and present approaches for adding new therapies to hospital/health system formularies to ensure timely access to newly approved therapies for SMA. SUMMARY: Advances in clinical care have significantly extended the lives of individuals with SMA, and research into the genetic mechanisms leading to disease have revealed strategies for intervention that target the underlying cause of SMA. Nusinersen is now on the market, and other treatment options, such as AVXS-101, may soon be approved. This article provides an overview of SMA and the genetic mechanisms leading to SMN deficiency, then describes how new and emerging treatments work to overcome this deficiency and prevent associated nerve damage and disability. In addition, we discuss steps for incorporating AVXS-101 into hospital/health system formularies, along with barriers and concerns that may delay access, based in part on lessons learned with nusinersen. Academy of Managed Care Pharmacy 2018-12 /pmc/articles/PMC10408414/ /pubmed/30582825 http://dx.doi.org/10.18553/jmcp.2018.24.12-a.s3 Text en Copyright © 2018, Academy of Managed Care Pharmacy. All rights reserved. https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Supplement
Rao, Vamshi K.
Kapp, Daniel
Schroth, Mary
Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title_full Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title_fullStr Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title_full_unstemmed Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title_short Gene Therapy for Spinal Muscular Atrophy: An Emerging Treatment Option for a Devastating Disease
title_sort gene therapy for spinal muscular atrophy: an emerging treatment option for a devastating disease
topic Supplement
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10408414/
https://www.ncbi.nlm.nih.gov/pubmed/30582825
http://dx.doi.org/10.18553/jmcp.2018.24.12-a.s3
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