Gene therapy in neuromuscular disorders

Abstract

Monogenic neuromuscular disorders are potentially treatable through gene therapy. Using viral vectors, a therapeutic transgene aims to restore normal levels of a protein not produced by the defective gene, or to silence a gene whose expression leads to toxic effects. Spinal Muscular Atrophy (SMA) is a good example of a monogenic disease that currently has an AAV9-based vector gene therapy as a therapeutic option. In this review, we intend to discuss the viral vectors and their mechanisms of action, in addition to reviewing the clinical trials that supported the approval of gene therapy (AVXS-101) for SMA as well as neuromuscular diseases that are potentially treatable with gene replacement therapy.

Resumo

Doenças neuromusculares monogênicas são potencialmente tratáveis através de terapia gênica. Utilizando-se de vetores virais, um transgene terapêutico objetiva repor os níveis normais de uma proteina não produzida pelo gene defeituoso ou silenciar um gene cuja expressão leva a efeitos tóxicos. A Atrofia Muscular Espinhal (AME) é um bom exemplo de doença monogenica que atualmente tem uma terapia gênica com vetor viral AAV9 como opção terapêutica. Nesta revisão, pretendemos discutir os vetores virais e macanismos de ação utilizados, além de revisar os ensaios clínicos que embasaram a aprovação da terapia gênica (AVXS-101) para AME, assim como doenças neuromusculares potencialmente tratáveis com terapia de reposição gênica.

Keywords:

Genetic Therapy - Dependovirus or Adeno-Associated Virus (AAVs) - Muscular Atrophy, Spinal - Survival of Motor Neuron 1 Protein - Genetic Vectors

Palavras-chave:

Terapia Genética - Dependovirus ou Virus Adeno-Associados (AAVs) - Atrofia Muscular Espinal - Proteína 1 de Sobrevivência do Neurônio Motor - Vetores Genéticos

Authors’ contributions:

RHM: responsible for reviewing the literature and drafting the article; RHM, EZ: made critical revision of the article and final approval of the version to be published.

Publication History

Received: 04 April 2022

Accepted: 29 April 2022

Article published online:
06 February 2023

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