Chronic sleep disruption is among the most frequently reported and disabling pathological features of Parkinson’s disease (PD). This loss of sleep quality is driven by dysregulation of the body’s daily circadian rhythms. Working with Biogen, we will evaluate a novel therapeutic tool that targets a core component involved in controlling the activity of the body’s biological clock. This component, a protein called CK1, plays a key role in regulating sleep and has been extensively characterized using pharmacological inhibitors — drugs that have been shown to rapidly restore disrupted sleep patterns.
We will assess whether well-timed inhibition of CK1 shows promise in improving sleep quality and reestablishing the circadian timing that is dysregulated in PD.
Using preclinical models of PD, we will determine whether administration of CK1 inhibitors in a carefully timed manner can restore healthy sleep parameters, sleep quality and the smooth functioning of the circadian clock. We will also assess whether improvements in sleep quality and circadian rhythm lead to a reduction in other physiological changes characteristic of PD, such as brain inflammation, alpha-synuclein accumulation and the death of dopamine-producing neurons.
Impact on Diagnosis/Treatment of Parkinson’s Disease:
Our studies will establish whether this exciting new therapeutic approach can improve sleep quality and restore overall circadian regulation in preclinical models of late-stage PD. In addition, we will determine whether this therapeutic tool can attenuate the pathological hallmarks of PD.
Next Steps for Development:
Demonstrating the therapeutic effectiveness of resetting circadian rhythms could foster the development of novel drugs for the treatment of PD. Our research, along with Biogen’s ongoing clinical studies targeting CK1, will reveal new roles for this target and more clearly define its future in PD treatment.