application): Inflammatory bowel disease (IBD) is a major source of chronic morbidity in the United States population. Current treatment regimens are of limited efficacy, as there are no entirely non-toxic pharmaceuticals which totally halt or reverse the progression of IBD. The applicant proposes to test the feasibility of a therapeutic, mercaptoethylguanidine (MEG), in a sub-human primate model of IBD. In experimental rodent models of IBD, when given as a post-treatment, MEG evidently provides near total protection from colonic injury. MEG owes its efficacy in IBD to its combined action as (1) a highly potent and selective inhibitor of the toxin-generating inducible nitric oxide synthase, and (2) a potent scavenger of peroxynitrite, a powerful oxidant produced in the colonic mucosa in IBD. The applicant proposes to establish proof-of-principle in a standard primate model of spontaneous IBD, as assessed by histology and biochemical correlates of tissue injury. Upon confirmation of MEG's efficacy in this stringent and clinically relevant model, the applicant intends to apply for Phase II SBIR funding to support formal toxicology studies and a Phase I FDA-regulated clinical trial.
The annual incidence of inflammatory bowel disease (IBD) in the United States is estimated at 200,000 patients. An effective, non-toxic therapy for IBD would command a unit price of $1,000. Accordingly, a $200 million domestic market is anticipated. Worldwide income would be approximately four times the domestic market.
