G6PD activation to restore dopamine levels in Parkinson’s Disease

Investigators: Scott Ryan

The protein, a-synuclein accumulates into aggregates in the brains of people with Parkinson’s Disease (PD) and is the primary component of Lewy Bodies. How accumulation of a-synuclein leads to loss of dopamine, the neurotransmitter responsible for initiating movement, is poorly understood. We have identified the metabolic enzyme G6PD as a novel risk gene associated with significant disease burden in people with PD.  G6PD is needed to protect dopamine from being oxidized in the brain.

Moreover, we have determined that a-synuclein aggregates reduce G6PD activity resulting in dopamine loss in both animal models of PD and in human neuron-derived PD patient stem cells. We propose to evaluate a novel G6PD activating drug candidate in these systems to determine if activating G6PD protects dopamine from the effects of a-synuclein aggregates, thereby slowing disease progression.