Development of a HT Screen to Identify Novel Modulators of the CRFBP
Overview A connection between the corticotropin signaling pathway and alcohol use disorder (AUD) has been shown previously. We developed a high throughput screen to identify small molecule modulators of this pathway as potential therapeutics for AUD. Market Opportunity Currently available treatments for alcohol use disorder (AUD) include three pharmacotherapies approved by the Food and Drug Administration: disulfiram, naltrexone, and acamprosate. The clinical efficacy of these pharmacotherapies is marginal, and they all suffer from limiting contraindications. Thus, there is a critical need for more effective pharmacotherapies for AUD. Innovation and Meaningful Advantages Growing attention has been paid to the stress system—specifically, the signaling pathway of corticotropin releasing factor (CRF)—as a pharmacological target for AUD, and the expression pattern of CRF binding protein (CRFBP) suggests a critical role in the modulation of the stress responses. Using a novel high throughput screen we developed, we were able to identify two negative allosteric modulators (NAMs) of CRFBP.
Commercial Development: Current State and Next Steps We transferred this novel biological assay to our collaborator’s robotic facility and have screened >350,000 compounds. We have selected 2 allosteric modulators and tested them in an ex vivo preclinical alcohol model.
Collaboration Opportunity Our goal is to collaborate with biopharma partners/funders who can bring into play the developmental, translational, and financial resources needed to advance this technology into the commercial marketplace.
Principal Investigator Carolina Haass-Koffler PhD Associate Professor of Psychiatry and Human Behavior Brown University Brown Tech ID #2579 carolina_haass-koffler@brown.edu
IP Information 2021-10-07; US 2021/0308107A1; published.
Publication Curley DE, et al., Corticotropin releasing factor binding protein as a novel target to restore brain homeostasis: lessons learned from alcohol use disorder research. Frontiers in Behavioral Neuroscience, section Motivation and Reward (in press) Haass-Koffler CL, et al., Defining the role of Corticotropin Releasing Factor Binding Protein in alcohol consumption, Translational Psychiatry 2016 PMID: 27845775, PMCID: PMC3434418