Epigenetic engineering to reverse the Parkinson’s expression state

Abstract

Nature, initiation and ensuing cellular propagation mode of sporadic Parkinson’s disease (comprising over 90% of all Parkinson’s cases) remain open research questions. Accordingly, so does the best therapeutic avenue for addressing this debilitating disease that today affects an estimated 7–10 million people worldwide. Recently, we argued that sporadic Parkinson’s be fundamentally characterized as a pathological deviation from normality in the expression program of a cell, the PD-state. Further, we suggested this generic cell state (not restricted to neurons) could be epigenetically locked-in. This raises the theoretical possibility of reverting a cell’s PD-state to normality by appropriate epigenetic reprogramming. In here, we propose an in vitro relatively high throughput search for a cocktail of molecules that induces an epigenetic reversal of the PD-state. A generic multi-tissue PD-state phenotype appears to be a defect on mitochondrial bioenergetics. In the above search, we suggest utilizing a metabolic challenge as a preliminary screen for assessing, via improvement of energy metabolism, reversal of the PD-state.