Gene Therapy Development and Validation for Huntington's Disease Fibro TG-HD
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- In vitro validation of a RNA trans-splicing gene therapy for the correction of supernumerary CAG repeats into fibroblasts derived from skin biopsies of patients with Huntington's disease.
研究概览
简要总结
Huntington's disease is a rare and fatal monogenic neurodegenerative disorder whose molecular origin is an expansion of CAG triplets within the first exon of the Huntingtin gene. Although a growing number of emerging therapies are in clinical trials, there are no proven neuroprotective or curative treatments approved by the health authorities, as they have not yet demonstrated any real therapeutic benefit or absence of toxicity. Trans-splicing gene therapy is defined as the correction of a mutated endogenous pre-messenger RNA by a therapeutic exogenous pre-messenger RNA. Trans-splicing is a suitable alternative approach, since it is capable of allelic selectivity and replacement of mutated sequences by the wild-type one, criteria that no therapy tested to date meets. This project involves the therapeutic validation of trans-splicing of Huntingtin gene transcripts, and will evaluate its therapeutic effects in vitro, into primary fibroblast cell lines derived from skin biopsies of Huntington's disease patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 ≤ age ≤ 70 years.
- •Signed written, free and informed consent to participate in the study.
- •Patients with a CAG≥36 allele (with reduced or full penetrance). penetrance)
- •People affiliated to or benefiting from a social security scheme.
排除标准
- •Individuals who have participated in a gene therapy trial using AAV, ASO, mi/si/shRNA administration, likely to disrupt expression, splicing of pre-mRNAs, mRNA splicing, mRNA expression/regulation/translation, energy or protein metabolism directly or indirectly linked to the Huntingtin gene (HTT), its transcripts and proteins.
- •Clinical or paraclinical elements that may suggest a differential diagnosis.
- •People unable to express their consent.
- •Pregnant, breast-feeding or parturient women
- •People deprived of liberty by administrative or judicial decision
- •People under legal protection (curatorship, guardianship).
研究组 & 干预措施
Huntington's patient
skin biopsy
干预措施: skin biopsy (Procedure)
结局指标
主要结局
In vitro validation of a RNA trans-splicing gene therapy for the correction of supernumerary CAG repeats into fibroblasts derived from skin biopsies of patients with Huntington's disease.
时间窗: At the inclusion
Correction of mutated endogenous transcripts.
次要结局
- Quantify the expression of Huntingtin protein (HTT) and its (in)usual protein partners.(At the inclusion)