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

Behav Brain Res. 2018 Jan 30;337:183-185. doi: 10.1016/j.bbr.2017.09.023. Epub 2017 Sep 14.


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.

Keywords: Bioavailable plasmalogen precursor; Dyskinesia; MPTP; PPI-1011; Parkinson’s disease.

MeSH terms

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


  • Antiparkinson Agents
  • Plasmalogens
  • phosphatidal ethanolamines
  • Levodopa