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A ROCK Inhibitor as a Neuroprotective Therapy for Parkinson's Disease

Study Rationale:
In the past, we demonstrated that using drugs to deactivate Rho-associated protein kinase (ROCK), a protein regulating shape and movement of cells, can protect dopamine-producing brain cells from damage caused by alpha-synuclein, a sticky protein that clumps in the brains of people with Parkinson's disease (PD). However, the optimal drug for ROCK deactivation in PD has not yet been identified.

Hypothesis:
We hypothesize that KL-00974, a drug candidate developed by Kadmon Holdings, Inc, with an improved ability to deactivate ROCK and low likelihood of having side effects, will protect dopamine-producing brain cells in pre-clinical models of Parkinson's.

Study Design:
We will evaluate the neuroprotective potential of KL-00974 in two pre-clinical models of Parkinson's with alpha-synuclein features, leveraging specific strengths of each of the models. The drug's ability to attenuate alpha-synuclein-induced brain inflammation and decrease alpha-synuclein clumping will also be evaluated.

Impact on Diagnosis/Treatment of Parkinson's disease:
This study could identify a new disease-modifying therapy for PD.

Next Steps for Development:
If the present study is successful, KL-00974 will be evaluated further in a clinical trial.


Researchers

  • Caryl E. Sortwell, PhD

    Grand Rapids, MI United States


  • Jeffrey P. MacKeigen, PhD

    Grand Rapids, MI United States


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