The present proposal stems from the observation that a number of molecules involved in NAD metabolism (enzymes, precursors and NAD itself; that we herein refer to as the NADome) are parodoxically also found extracellularly. Importantly, the proposers have developed a monoclonal antibody targeting one of these extracellular enzymes, nicotinamide phosphoribosyl transferase (NAMPT), and have found it to significantly reduce the symptoms/damage in two separate murine models of inflammatory bowel disease. This is paralled by the observation that this enzyme, as well as other NADome members, are significantly elevated in acute and chronic inflammatory states.
The consortium has therefore been built to develop new enabling technologies to gain further knowledge on the extracellular NADome and to apply this to the development of new therapeutic strategies in inflammatory bowel disease, a clinical condition in which many patients still cannot find a suitable pharmacological answer to their symptoms.