Seven Solutions for Neuroprotection in Parkinson's Disease.

Abstract

Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra and accumulation of iron and alpha-synuclein; it follows a characteristic pattern throughout the nervous system. Despite decades of successful preclinical neuroprotective studies, no drug has then shown efficacy in clinical trials. Considering this dilemma, we have reviewed and organized solutions of varying importance that can be exclusive or additive, and we outline approaches to help generate successful development of neuroprotective drugs for PD: (1) select patients in which the targeted mechanism is involved in the pathological process associated with the monitoring of target engagement, (2) combine treatments that target multiple pathways, (3) establish earliest interventions and develop better prodromal biomarkers, (4) adopt rigorous methodology and specific disease-relevant designs for disease-modifying clinical trials, (5) customize drug with better brain biodistribution, (6) prioritize repurposed drugs as a first line approach, and (7) adapt preclinical models to the targeted mechanisms with translational biomarkers to increase their predictive value. © 2020 International Parkinson and Movement Disorder Society.

• Authors: David Devos, Etienne Hirsch, Richard Wyse
• Journal: Movement disorders : official journal of the Movement Disorder Society (Mov Disord) Vol. 36 Issue 2 Pg. 306-316 (02 2021) ISSN: 1531-8257 [Electronic] United States
• PMID: 33184908 (Publication Type: Journal Article, Review)
• Copyright: © 2020 International Parkinson and Movement Disorder Society.

Chemical References

• Neuroprotective Agents
• alpha-Synuclein

Topics

• Humans
• Neuroprotection
• Neuroprotective Agents (pharmacology, therapeutic use)
• Parkinson Disease (drug therapy)
• Substantia Nigra (metabolism)
• Tissue Distribution
• alpha-Synuclein (metabolism)