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Funded Studies

Reconstituting the Lost Nigrostriatal Circuitry in Parkinson’s Disease

Study Rationale:
We recently discovered that it is possible to generate new neurons to rebuild the damage neural circuitries in a Parkinson’s disease model. This establishes a new foundation for developing strategies to reverse the disease. Our proposed project will investigate how to change a cell’s identity to encourage it to become a neuron, how to make the right new type of neurons in the brain to rebuild different circuitries, and how to make new neurons that will not become sick again.

We hypothesize that astrocytes, an abundant population of non-neuronal cells in the brain, store a latent program that allows them to become neurons if the right types of inducing signals are provided.

Study Design:
We have designed five sets of experiments to address a series of fundamental questions on cell fate determination and reprogramming. We will analyze individual cells to elucidate key regulatory events responsible for those cells to become neurons. We will search for critical genes that make cell fate change less efficient so that we can improve the reprogramming efficiency by inhibiting the function of those genes. We will examine reprogramming in different brain regions to test their benefits to both motor and non-motor symptoms and develop strategies to make new and disease-resistant neurons.

Impact on Diagnosis/Treatment of Parkinson’s Disease:
More information on cellular reprogramming will pave the way to rebuilding the neural circuitries lost to degeneration. If successful, this will lead to the development of a completely new cell replacement therapy against Parkinson’s disease.

Next Steps for Development:
The next step is to translate the basic science findings for development of a set of reagents that can be tested for efficacy and safety to prepare for clinical trials.


  • William C. Mobley, MD, PhD

    La Jolla, CA United States

  • Xiang-Dong Fu, PhD

    La Jolla, CA United States

  • William C. Mobley, MD, PhD

    La Jolla, CA United States

  • Yuanchao Xue, PhD

    Beijing China

  • Steven F. Dowdy, PhD

    La Jolla, CA United States

  • Allen Wang, PhD

    La Jolla, CA United States

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