학술논문

Therapeutic strategies for Parkinson’s disease: promising agents in early clinical development
Document Type
Article
Source
Expert Opinion on Investigational Drugs; November 2020, Vol. 29 Issue: 11 p1249-1267, 19p
Subject
Language
ISSN
13543784; 17447658
Abstract
ABSTRACTIntroductionTo date, no drug has demonstrated clinically indisputable neuroprotective efficacy in Parkinson’s disease (PD). We also have no effective symptomatic treatment for disabling symptoms such as balance problems, and dementia, and we need to improve the efficacy and safety profile of drugs currently used in the management of motor complications.Areas coveredWe examine the agents which appear to have most therapeutic promise based on concepts, feasibility in a reasonable time frame, and available clinical data and place an emphasis on disease-modifying treatments. PUBMED and Clinicaltrials.gov databases were searched for Phase I and II randomized trials for symptomatic or disease-modifying treatments considering only studies that began since 2010 or that were completed after 2015, up to 30 April 2020.Expert opinionEncouraging progress has been made in our understanding of molecular pathways. We find passive immunization approaches against α-synuclein, LRRK2 kinase inhibitors, and treatment that can increase GCase activity, which have shown some efficacy on both GBA-mutated and non-mutated PD patients. The recognition of non-dopaminergic impairment and the prominent role of non-motor symptoms have prompted the development of trials on compounds that could tackle different neurotransmitter systems. Future approaches will encompass more personalized medicine strategies based on molecular signatures and non-motor phenotypes.