Lowering the HTT1a transcript as an effective therapy for Huntington's disease in a knockin mouse model - PubMed
5 hours ago
- #siRNA therapy
- #HTT1a transcript
- #Huntington's disease
- Lowering HTT1a transcript is an effective therapy for Huntington's disease (HD) in a knockin mouse model.
- HD is caused by a CAG repeat expansion in exon 1 of the HTT gene, leading to somatic expansion and disease progression.
- HTT1a transcript and protein are highly aggregation-prone and pathogenic, increasing with CAG repeat expansion.
- siRNAs targeting Htt1a (634/486) and full-length Htt (10150) were compared for efficacy in zQ175 and wild-type mice.
- Targeting Htt1a was more effective at delaying HTT aggregation and transcriptional dysregulation than targeting full-length Htt.
- The study supports HTT-lowering strategies focusing on HTT1a transcript, either alone or with full-length HTT.