Project description
Innovative screening for drug efficacy modulation by circadian clocks
The internal circadian clocks set the timing for circadian rhythms, regulating human body processes such as sleep/wake cycles, hormonal activity, temperature rhythm, and eating and digesting. The disruption of circadian clocks is associated with a broad spectrum of diseases, from sleep disorders to cancer. Therapeutic drug targets could be influenced by circadian clocks, and the timing of drug administration can maximise the drug’s efficacy. The EU-funded CircaSCOPE project proposes an innovative high throughput methodology for the construction of high-resolution phase transition curves for the screening of clock-modulating drugs. The developed methodology will improve drug discovery, targeting diseases associated with circadian disruption, and identifying drugs with the side effects affecting the clocks.
Objective
Circadian clocks carry an immense importance to human health, as clock disruption is related to various malignancies from sleep disorders through diabetes to cancer. Furthermore, many drug targets are influenced by circadian clocks. In order to maximize drug’s efficacy while minimizing side effects, it is necessary to consider the drug’s time-of-administration, also known as “chronotherapy”. These revelations are critical for drug administration and development. However, their practical implementation is tempered by the lack of suitable research tools that bridge the gap from the bench to the clinic.
The time-dependent effect of an intervention on the clock is represented by the Phase Transition Curve (PTC). PTCs retrieval is laborious and challenging, consequently they were mostly overlooked in the pharmaceutical R&D process. In the ERC Project CIRCOMMUNICATION, we studied clock-resetting mechanisms, which led to the development of CircaSCOPE, an efficient high-throughput methodology for high-resolution PTC construction.
CircaSCOPE can be used as a powerful screening method for clock-modulating drugs, either for the purpose of targeting pathologies associated with circadian disruption, or to identify drugs which elicit unwanted side-effects on the clock. ¬Once fully developed and systematically integrated in chrono-medicine, CircaSCOPE has the potential to improve drug discovery and yield medicines with better therapeutic index.
Here, we detail our plan for the first steps toward commercializing of our innovation. We will demonstrate the applicability of this approach through drug libraries screens and expand the repertoire of cell types that the system relies on. In addition, we will explore different commercialization strategies and interact with potential stakeholders and end-users. Given the medical importance of circadian effects, we’d envisage that CircaSCOPE will become as a gold-standard procedure in future drugs development.
Fields of science
- medical and health sciencesclinical medicinepsychiatrysleep disorders
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepathology
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-AG-LS - HORIZON Lump Sum GrantHost institution
7610001 Rehovot
Israel