The plasmalogen precursor analog PPI-1011 reduces the development of L-DOPA-induced dyskinesias in de novo MPTP monkeys.

Abstract

The gold standard therapy for Parkinson's disease (PD), L-3,4-dihydroxyphenylalanine (L-DOPA), induces dyskinesias in the majority of patients after years of treatment. Ethanolamine plasmalogens (PlsEtn) play critical roles in membrane structure mediated functions and as a storage depot of polyunsaturated fatty acids such as docosahexaenoic acid. We previously showed that a PlsEtn precursor PPI-1011 reduced already established L-DOPA-induced dyskinesias (LID) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesioned monkeys as a PD model. We hypothesize that development of LID can be prevented with a PPI-1011 treatment in de novo MPTP-lesioned monkeys. MPTP-lesioned monkeys were treated once daily for 28days with either L-DOPA or L-DOPA+PPI-1011 (25mg/kg). The antiparkinsonian effect of L-DOPA was maintained throughout the treatment period in MPTP-lesioned monkeys treated with L-DOPA alone and L-DOPA+PPI-1011. Over the 28days of treatment, the mean dyskinesia score increased in L-DOPA-treated monkeys whereas this increase was significantly less in the L-DOPA+PPI-1011 group. This was followed by a washout period of 2 weeks of both experimental groups without treatment. Then both groups were administered once during week 7 and twice during week 8 with L-DOPA with behavioral measures recorded on treatment days. MPTP monkeys of both experimental groups administered L-DOPA in experimental week 7 showed reduced LID. During week 8, the L-DOPA group showed increased LID whereas LID remained low in the group previously treated with L-DOPA+PPI-1011. The present results suggest that PPI-1011 can prevent/delay the development of LID while maintaining the antiparkinsonian activity of L-DOPA.

• Authors: Mélanie Bourque, Laurent Grégoire, Thérèse Di Paolo
• Journal: Behavioural brain research (Behav Brain Res) Vol. 337 Pg. 183-185 (Jan 30 2018) ISSN: 1872-7549 [Electronic] Netherlands
• PMID: 28917506 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Antiparkinson Agents
• Plasmalogens
• phosphatidal ethanolamines
• Levodopa

Topics

• Animals
• Antiparkinson Agents (adverse effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Dyskinesia, Drug-Induced (drug therapy, etiology)
• Female
• Levodopa (adverse effects)
• MPTP Poisoning (drug therapy)
• Macaca fascicularis
• Ovariectomy
• Plasmalogens (therapeutic use)
• Time Factors