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Pre-commercialization of circadian clock-drug interactions screening tool for therapeutic applications

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 drugs efficacy while minimizing side effects, it is necessary to consider the drugs 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, wed envisage that CircaSCOPE will become as a gold-standard procedure in future drugs development.

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Topic(s)

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HORIZON-ERC-POC - HORIZON ERC Proof of Concept Grants

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Call for proposal

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(opens in new window) ERC-2022-POC1

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Host institution

WEIZMANN INSTITUTE OF SCIENCE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 150 000,00
Address
HERZL STREET 234
7610001 Rehovot
Israel

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Activity type
Higher or Secondary Education Establishments
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Total cost

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Beneficiaries (1)

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