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.
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.
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.