Branaplam como um Promissor Modulador de Splicing: Da Atrofia Muscular Espinhal à Doença de Huntington

Autores

  • Beatriz Garrido Faculty of Medicine / University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-3789-4920
  • Joana Afonso Ribeiro Center for Child Development – Neuropediatrics Unit / Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal https://orcid.org/0000-0001-5712-3106
  • Filipe Palavra Center for Child Development – Neuropediatrics Unit; Institute of Pharmacology and Experimental Therapeutics, Coimbra Institute for Clinical and Biomedical Research (iCBR); Clinical Academic Center of Coimbra / Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra; Faculty of Medicine, University of Coimbra, Coimbra, Portugal https://orcid.org/0000-0002-2165-130X

DOI:

https://doi.org/10.46531/sinapse/AR/230005/2023

Palavras-chave:

Atrofia Muscular Espinhal/ tratamento, Doença de Huntington/ tratamento, Éxons/genética, Splicing RNA/efeitos dos fármacos, Splicing Alternativo

Resumo

Os moduladores de splicing, que têm como alvo o RNA, revolucionaram a medicina moderna ao permitirem a regulação de expressão genética de forma reversível. A primeira molécula encontrada com a capacidade de alterar um processo de splicing particular num local específico foi o branaplam. Inicialmente, o branaplam foi desenvolvido como um modulador de splicing para a atrofia muscular espinhal (AME), a segunda doença autossómica recessiva mais comum e a principal causa de mortalidade infantil genética. Mais recentemente, foi investigada a sua utilização na doença de Huntington (DH), uma doença neurodegenerativa autossómica dominante fatal, com controlo sintomático limitado. Nesta revisão analisa-se, de forma abrangente, o programa de desenvolvimento do branaplam em ambas as situações clínicas mencionadas, projetando-se alguns dos aspetos que podem carecer de investigação futura, quando se consideram os moduladores de splicing, como classe terapêutica, nestas doenças.

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Publicado

2023-07-18

Como Citar

1.
Garrido B, Afonso Ribeiro J, Palavra F. Branaplam como um Promissor Modulador de Splicing: Da Atrofia Muscular Espinhal à Doença de Huntington. Sinapse [Internet]. 18 de Julho de 2023 [citado 11 de Outubro de 2024];23(2):82-91. Disponível em: https://sinapse.pt/index.php/journal/article/view/21

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