Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic.
Mol Ther
; 26(4): 947-962, 2018 04 04.
Article
em En
| MEDLINE
| ID: mdl-29503201
ABSTRACT
The single mutation underlying the fatal neuropathology of Huntington's disease (HD) is a CAG triplet expansion in exon 1 of the huntingtin (HTT) gene, which gives rise to a toxic mutant HTT protein. There have been a number of not yet successful therapeutic advances in the treatment of HD. The current excitement in the HD field is due to the recent development of therapies targeting the culprit of HD either at the DNA or RNA level to reduce the overall mutant HTT protein. In this review, we briefly describe short-term and long-term HTT-lowering strategies targeting HTT transcripts. One of the most advanced HTT-lowering strategies is a microRNA (miRNA)-based gene therapy delivered by a single administration of an adeno-associated viral (AAV) vector to the HD patient. We outline the outcome measures for the miRNA-based HTT-lowering therapy in the context of preclinical evaluation in HD animal and cell models. We highlight the strengths and ongoing queries of the HTT-lowering gene therapy as an HD intervention with a potential disease-modifying effect. This review provides a perspective on the fast-developing HTT-lowering therapies for HD and their translation to the clinic based on existing knowledge in preclinical models.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Doença de Huntington
/
MicroRNAs
/
Pesquisa Translacional Biomédica
/
Proteína Huntingtina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article