Cell therapy holds promise for debilitating brain disorders like Parkinson’s disease (PD). In order for cell therapy to achieve its goal, transplanted nerve cells need to reach their target and reconstruct a circuit that is specific to lost function. This strategy is challenging in the adult brain where the environment is not particularly conducive to the transplant and growth of neurons.
We have recently discovered that when dopamine neurons derived from human embryonic stern cells are transplanted into an area of the midbrain called the substantia nigra, they project nerves into the brain’s striatum and reconstruct the nigra-striatal circuit within six months. This repaired circuit has corrected motor deficits in mouse models of Parkinson’s disease.
Translation of this strategy to human patients is daunting as the nigra-striatal distance in humans is at least 10 times longer than in mice. We propose overcoming this barrier by engineering monkey stem cells with a receptor activated by a designer drug, differentiating those cells into dopamine neurons, and “pulling” the nerves toward the striatum by chronic application of the designer drug after the neurons are transplanted into a monkey model of Parkinson’s disease.
If successful, this study will serve as a preclinical setting for future treatments for Parkinson’s disease and other neurological conditions.