Branaplam como um Promissor Modulador de Splicing: Da Atrofia Muscular Espinhal à Doença de Huntington
DOI:
https://doi.org/10.46531/sinapse/AR/230005/2023Palavras-chave:
Atrofia Muscular Espinhal/ tratamento, Doença de Huntington/ tratamento, Éxons/genética, Splicing RNA/efeitos dos fármacos, Splicing AlternativoResumo
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.Downloads
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