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

The plasmalogen precursor analog PPI-1011 reduces the development of L-DOPA-induced dyskinesias in de novo MPTP monkeys. Behav Brain Res. 2017 Sep 13;: Authors: Bourque M, Grégoire L, Di Paolo T 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 t...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research