Objective: The aim of this study is to make preclinical mice models for disease-modifying therapies in Parkinson’s disease.

Background: The prodromal stage of Parkinson’s disease (PD) provides an excellent opportunity for disease-modifying therapies (DMTs), and animal models for prodromal PD are urgently needed. Genetic studies showed that the increased expression of α-synuclein (αS) is closely linked to the development of idiopathic PD, and clinical studies in fetal dopaminergic cell transplantation and experimental animal studies suggest αS propagation as one of the possible mechanism underlying the progression of PD.

Method: We generated BAC transgenic mice with A53T mutation and three risk polymorphisms identified in PD to make a prodromal PD mice model. In addition, we injected αS fibrils into the unilateral striatum of these BAC transgenic mice to make symptomatic PD mice model.

Results: The A53T SNCA BAC transgenic mice expressed pathological αS accumulation and concomitant DA neuronal loss in the substantia nigra pars compacta (SNpc) without locomotor dysfunction. They exhibited RBD-like behavior as well as hyposmia, and are thus considered as prodromal PD mice model. Furthermore, they are sensitive to exogenous αS fibril injection, and they exhibited around 40 % DA neuronal loss with αS aggregation in the SNpc 2 months after injection of αS fibrils into the unilateral striatum.

Conclusion: The A53T SNCA BAC transgenic mice with or without αS fibril injection can be a valuable model for the preclinical studies of DMTs in PD.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/alpha-synuclein-bac-transgenic-mice-as-a-preclinical-model-for-disease-modifying-therapies-in-parkinsons-disease/