Study Rationale: Disrupted sleep is an early sign of Parkinson’s disease (PD) that worsens as the disease progresses. Chronic symptoms of PD include alternations in sleep patterns and changes in the body’s internal clock, or circadian rhythm. The internal timekeeping of circadian rhythm is controlled by a protein called casein kinase 1 delta (CK1d). Inhibitors of CK1d may resolve circadian disruptions and improve sleep patterns in people with PD, and we have made exciting progress in the development of such a molecule. We are seeking to evaluate our molecule in preclinical models to determine whether this molecule could help people with PD.
Hypothesis: We hypothesize that modulating the internal circadian clock with NMRA-070, a compound that inhibits CK1d, will reverse sleep alterations in PD and could ultimately treat symptoms and prevent PD progression by altering alpha-synuclein pathology.
Study Design: We will validate sleep and circadian alterations in well characterized preclinical models of PD to identify the appropriate model for evaluating whether our drug candidate, NMRA-070, modulates these phenotype(s). We will use quantitative electroencephalography (qEEG) to monitor sleep quality in the various PD models and determine whether NMRA-070 alters the qEEG measures. If NMRA-070 also alters the pathological state of alpha-synuclein in cell models or rodent models, CK1d inhibition could prove effective at modifying the course of the disease.
Impact on Diagnosis/Treatment of Parkinson’s disease: If successful, this work could significantly impact the treatment of PD as it will be critical for determining whether NMRA-070 should be advanced to clinical trials to treat the sleep-related symptoms of people with PD. It will also demonstrate whether qEEG could serve as readout of drug effectiveness in people.
Next Steps for Development: The next steps would be to develop clinical protocols and methods for measuring qEEG in people with PD to determine whether NMRA-070 has the potential to be a symptomatic treatment.