Connexin hemichannels and pannexin channels mediate the exchange of biochemical messengers between the cytosol of a cell and its extracellular environment. This type of cellular communication underlies cell death and inflammation, both which are associated with a plethora of diseases. Closing connexin hemichannels and pannexin channels therefore seems an interesting therapeutic strategy. In this respect, the ERC Starting Grant project CONNECT has demonstrated that peptide-based inhibition of Cx32 and Cx43 hemichannels as well as of Panx1 channels counteracts the manifestation of acute and chronic liver disease. However, these peptides cope with stability issues thus impeding clinical application. No other types of connexin hemichannel and pannexin channel inhibitors are available today despite their promising therapeutic potential. The present CONNECT-2-CLINIC project will meet this urgent need by generating specific and in vivo-applicable connexin hemichannel and pannexin channel inhibitors. These new inhibitors will be tested in vitro for their capacity to inhibit their target channels and to reduce inflammation. They will be subsequently tested in human-relevant mouse models of acute liver failure and non-alcoholic steatohepatitis. This dual technology track will be aligned by a 3-phase business track in order to analyze and create market value. By doing so, the CONNECT-2-CLINIC project will provide solid proof-of-concept for further pharmaceutical development and clinical application.
|Effective start/end date||1/01/20 → 31/12/21|
Flemish discipline codes
- liver disease