Efficient treatment of Parkinson’s disease using ultrasonography-guided rhFGF20 proteoliposomes

Drug Delivery

Xiaomin Zhang¹  Xinyu Zhao¹  Lintao Song¹  Deli Zhuge¹  Zhifeng Huang¹  Feng Xia¹  Yingzheng Zhao¹  Junjun Xie¹  Kaiwen Guo¹  Jianlou Niu¹  Xiaokun Li¹ 

[1] School of Pharmaceutical Sciences & Center for Structural Biology, Wenzhou Medical University, Wenzhou, Zhejiang, Chin;

关键词: FGF20;    Parkinson’s disease;    focused ultrasound;    liposome;   

DOI  :  10.1080/10717544.2018.1482972

来源: publisher

【 摘 要 】

Fibroblast growth factor-20 (FGF20) is a paracrine member of the FGF family that is preferentially expressed in the substantia nigra pars compacta (SNpc). Previous studies have demonstrated that FGF20 enhances the survival of dopaminergic neurons suggesting the potential use of FGF20 to treat Parkinson’s disease (PD). However, the reduced solubility of the bacterial recombinant human FGF20 (rhFGF20) and the absence of efficient strategies to transport rhFGF20 across the blood–brain barrier (BBB) have halted its clinical application. In the present study, we have examined the efficiency of fuzing a small ubiquitin-related modifier (SUMO) to rhFGF20 to enhance its soluble expression and further investigated the efficacy of FUS-guided, rhFGF20-liposome transport across the BBB. We also examined the bioavailability and behavioral improvement in a 6-hydroxydopamine-lesioned rat model of PD following 2 weeks’ FUS-liposomal combinatorial treatment. Our results showed that, in contrast with rhFGF20 or LIP-FGF20, the FUS-LIP-rhFGF20 treatment could significantly improve the apomorphine-induced rotations by protecting against the loss of dopaminergic neurons in the SNpc. Our Results suggest that our combinatorial method would help overcome key challenges that hinder the currently available methods for the use of rhFGF20 in PD treatment.

【 授权许可】

CC BY