Modulation of Mitochondrial Respiration to Treat Colitis

The increase in inflammatory bowel disease (IBD) among veterans in recent years presents a significant clinical problem in the VA healthcare system. Major concerns for IBD veteran patients are the increased disease morbidity and risk of therapies. Further research is needed to develop safe and effective agents that enhance mucosal repair and reduce immune-suppression. Previous work from our lab has indicates that mitochondrial respiration promotes ulcer healing. This finding led us to postulate that increasing mitochondrial respiration constitutes a novel therapeutic goal in IBD. To improve mitochondrial function in IBD, we developed AuPhos, an oral agent that enhances mitochondrial electron transport that potentiates mitochondrial bio-energetics and mitochondrial reactive oxygen species (mtROS) production. The current project will ascertain the impact of this novel gold compound (AuPhos) on mitochondrial function and ulcer healing in mouse models of colitis as well as biopsy tissue explants from veterans with IBD.