Neuroprotectin D1 (NPD1) as a Disease-modifying Therapy for Parkinsonís Disease
Rapid Response Innovation Awards, 2013
Objective/Rationale: † † † † † ††
Progressive loss of dopaminergic neurons in Parkinsonís disease (PD) involves several pathogenic mechanisms. It may be assumed that drugs acting on more than one pathway should offer a therapeutic advantage. A novel class of homeostatic mediators called resolvins/protectins, which regulate inflammation, but also promote cell survival through multiple actions, may be one such option. The current objective is to investigate the neuroprotective efficacy of one particular member in this class of mediators, Neuroprotectin D1 (NPD1), in a pre-clinical model of PD.
Project Description: † † † † † † †
The potential of NPD1 to protect dopaminergic neurons will be investigated in a modified, chronic MPTP model with treatment beginning after initiation of dopaminergic neuron loss. In addition to prevention of continued neuron loss and potential sparing of dopaminergic pathways, mechanisms regulating inflammation and microglial activity, and pro-survival actions will be investigated.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † †
No therapy currently exists that will slow progression of PD. Existing data indicate that NPD1 has the potential to modify several pathogenic mechanisms of relevance in PD. If our hypothesis is confirmed, resolvins/protectins could represent a novel treatment paradigm for PD, with NPD1 as the first-in-class development candidate.
Anticipated Outcome: † † † † ††
An expected positive outcome will trigger the continued exploration of the therapeutic benefits of NPD1 in a broader subset of PD specific models, as well as lead to the initiation of development efforts to bring NPD1 on a path to clinical development.
Data analysis is currently ongoing but the initial impression is that disease induction, loss of dopamine neurons, became more aggressive than projected based on published data, which guided the model implementation. With 65% loss of dopamine neurons in controls, and NPD1 treatment initiated one week after lesion-induction with MPTP + probenecid, the rapid course of neuron loss may not have been appropriate for the mode of action of NPD1. There does not seem to be any sparing of dopamine neurons compared to controls, but for non-dopamine neurons a clear trend to reduced neuron loss was seen. Presently, the data is viewed as inconclusive with respect to a therapeutic potential for NPD1 in Parkinsonís disease. Further analysis is ongoing.
Senior Principal Scientist at PsychoGenics Inc.
Location: Tarrytown, New York, United States
Chief Scientific Officer and President at Anida Pharma Inc.
Location: Cambridge, Massachusetts, United States