Speaker: Prof. Lu Zhonghua, Shenzhen Institute of Advanced Technology, Chinese Academy oF Sciences

Time: 15:00-16:30 p.m., July 1, 2024, GMT+8

Venue: Rm B101, Lui Che-woo Building , PKU

Abstract: 

Gene therapy is a promising approach to treat brain disorders. For Parkinson's disease (PD), its symptoms are typically treated with levodopa or dopamine receptor agonists, but their action lacks specificity due to the wide distribution of dopamine receptors in the central nervous system and the periphery. Here, we report the development of a gene therapy strategy to selectively manipulate PD-affected circuitry. Targeting striatal D1 medium spiny neurons (MSNs), whose activity is chronically suppressed in PD, we engineered a therapeutic strategy comprised of a highly efficient novel retrograde AAV, promoter elements with strong D1-MSN activity, and a chemogenetic effector to enable precise D1-MSN activation after systemic ligand administration.
Application of this therapeutic approach rescues locomotion, tremor, and motor skill defects in both mouse and primate models of PD, supporting the feasibility of targeted circuit modulation tools for the treatment of PD in humans. In a second study, we developed a 120-bp ultra-compact promoter that can drive selective neuronal expression of therapeutic gene cargos in both rodent and nonhuman primate brains.

Source: School of Life Sciences, PKU