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URMC-099 in an In Vivo AAV-hSYN Model of Parkinson’s Disease

Study Rationale:
Parkinson's disease (PD) can be modeled by over-expressing human synuclein, a protein that can clump together to disrupt normal signaling in dopamine-containing neurons, which in turn leads to neurologic dysfunction associated with PD. This is associated with activation of the enzyme mixed lineage kinase type 3 (MLK3) in brain immune cells known as microglia and leads to neuroinflammation and death of dopamine neurons. Drugs that block MLK3 may delay or even reverse the onset and progression of PD.

We hypothesize that reversing the activation of brain immune cells with an MLK3 inhibitor can reverse the disease course of PD.

Study Design:
We will use the AAV virus to deliver excess amounts of human alpha-synuclein to dopamine neurons in laboratory models, followed by treatment with an experimental MLK3 inhibitor called URMC-099. We will test whether this treatment changes motor symptoms during the course of disease development, and we will examine brain regions for evidence of protection from alpha-synuclein damage. Additionally, we will determine how drug levels of URMC-099 in brain and blood correlate with neurologic and pathologic improvement in the models that have disease-causing levels of human alpha-synuclein in their dopamine neurons.

Impact on Diagnosis/Treatment of Parkinson's Disease:
By reversing levels of brain inflammation and dopamine nerve cell death, URMC-099 may offer an entirely new type of treatment.

Next Steps for Development:
URMC-099 is approximately halfway through safety testing before submission of an application for first-in-human trials with the U.S. Food and Drug Administration. Positive results in this pilot project could be used to obtain further funding to help design clinical trials for people with PD.


  • Malú G. Tansey, PhD

    Gainesville, FL United States

  • Harris A. Gelbard, MD, PhD

    Rochester, NY United States

  • Fredric P. Manfredsson, PhD

    Phoenix, AZ United States

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