中国科学院深圳先进技术研究院路中华等研究人员合作发现，回路特异性基因疗法可逆转灵长类帕金森病模型的核心症状。相关论文于2023年11月2日在线发表在《细胞》杂志上。

研究人员报告了一种基因治疗策略的开发情况，该策略可选择性地操纵受帕金森病（PD）影响的回路。纹状体D1中刺神经元（MSN）的活性在PD中长期受到抑制，针对这一靶点，研究人员设计了一种治疗策略，该策略由高效逆行腺相关病毒（AAV）、具有强D1-MSN活性的启动子元件和化学基因效应物组成，可在全身配体给药后精确激活D1-MSN。

应用这种治疗方法可以挽救小鼠和灵长类动物PD模型中的运动、震颤和运动技能缺陷，从而支持将靶向回路调节工具用于治疗人类PD的可行性。

据介绍，PD是一种使人衰弱的神经退行性疾病。其症状通常由左旋多巴或多巴胺受体激动剂治疗，但由于多巴胺受体广泛分布于中枢神经系统和外周，其作用缺乏特异性。

附：英文原文

Title: Circuit-specific gene therapy reverses core symptoms in a primate Parkinson’s disease model

Author: Yefei Chen, Zexuan Hong, Jingyi Wang, Kunlin Liu, Jing Liu, Jianbang Lin, Shijing Feng, Tianhui Zhang, Liang Shan, Taian Liu, Pinyue Guo, Yunping Lin, Tian Li, Qian Chen, Xiaodan Jiang, Anan Li, Xiang Li, Yuantao Li, Jonathan J. Wilde, Jin Bao, Ji Dai, Zhonghua Lu

Issue&Volume: 2023-11-02

Abstract: Parkinson’s disease (PD) is a debilitating neurodegenerative disorder. Its symptomsare typically treated with levodopa or dopamine receptor agonists, but its actionlacks specificity due to the wide distribution of dopamine receptors in the centralnervous system and periphery. Here, we report the development of a gene therapy strategyto selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spinyneurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeuticstrategy comprised of a highly efficient retrograde adeno-associated virus (AAV),promoter elements with strong D1-MSN activity, and a chemogenetic effector to enableprecise D1-MSN activation after systemic ligand administration. Application of thistherapeutic approach rescues locomotion, tremor, and motor skill defects in both mouseand primate models of PD, supporting the feasibility of targeted circuit modulationtools for the treatment of PD in humans.

DOI: 10.1016/j.cell.2023.10.004

Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01086-3

期刊信息

Cell：《细胞》，创刊于1974年。隶属于细胞出版社，最新IF：66.85

官方网址：https://www.cell.com/

投稿链接：https://www.editorialmanager.com/cell/default.aspx