Análise dos procedimentos e eficácia da terapia gênica AMT-130 para tratamento da doença de huntington: uma revisão sistemática
DOI:
https://doi.org/10.55892/jrg.v8i19.2640Palabras clave:
Terapia Gênica, AMT-130, AAV5-miHTT, Doença de Huntington, Proteína HuntingtinaResumen
A Doença de Huntington (DH) é uma desordem neurodegenerativa fatal sem terapias que modifiquem seu curso, sendo o tratamento atual limitado ao manejo sintomático. A terapia gênica AMT-130 surge como uma abordagem promissora, utilizando um vetor de vírus adeno-associado (AAV5) para entregar um microRNA (miRNA) que visa o RNA mensageiro da huntingtina (HTT), buscando a supressão duradoura da proteína mutante (mHTT) após uma única administração neurocirúrgica. Objetivou-se analisar e sintetizar as evidências sobre os procedimentos, eficácia, segurança e desafios associados à terapia AMT-130 para o tratamento da DH. Realizou-se uma busca sistemática nas bases de dados PubMed, Scopus, Embase, Web of Science e em registros de ensaios clínicos nas plataformas ClinicalTrials.gov e EU Clinical Trials Register, seguindo as diretrizes PRISMA e SWiM para a síntese narrativa dos dados. A análise foi estruturada em eixos temáticos derivados da Análise de Conteúdo de Bardin. Estudos pré-clínicos em múltiplos modelos animais demonstraram ampla biodistribuição do vetor e redução significativa da mHTT, com consequente melhora funcional e de sobrevida. Dados clínicos preliminares de ensaios de Fase I/II, embora com amostra reduzida, mostraram uma redução no biomarcador de neurodegeneração neurofilamento de cadeia leve (NfL) e um abrandamento na progressão da doença em comparação com coortes de história natural. O perfil de segurança é considerado gerenciável, com a ocorrência de neuroinflamação dose-dependente sendo o principal evento adverso grave, mitigado com o uso de imunossupressão. Infere-se que a AMT-130 representa um avanço pioneiro, demonstrando benefício biológico e funcional. No entanto, desafios como a via de administração invasiva, a natureza irreversível da terapia e as incertezas sobre a supressão não seletiva da huntingtina selvagem exigem uma interpretação cautelosa dos resultados promissores.
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