Molecular therapy : the journal of the American Society of Gene Therapy
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Review
Translation of MicroRNA-Based Huntingtin-Lowering Therapies from Preclinical Studies to the Clinic.
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. ⋯ 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.