Inflammatory bowel disease (IBD) is a collective term encompassing Crohn's disease and ulcerative colitis. Currently employed therapies directed at limiting chronic inflammation that have wide ranging affects on the immune system and serious side effect profiles. Despite recent advances in our understanding of intestinal immune mechanisms, medical therapy is often ineffective and surgical intervention is frequently necessary to treat complications of ongoing inflammation such as bowel obstruction, fistulae formation and cancer. Interleukin-1 is a proinflammatory cytokine that is fundamental to the ongoing inflammation in IBD with wide ranging effects on every arm of the immune response. Its naturally occurring antagonist, interleukin-1 receptor antagonist protein (IL-1ra), effectively inhibits the proinflammatory effects of IL-1. The long term objective of this proposal is to develop an alternative to conventional drug therapies; oral formulations of recombinant adenoviral vectors containing the transgene for IL-1ra. This vector is biologically active both in vitro and in vivo, and is capable of expressing therapeutic levels of IL-1ra. This phase II portion of this proposal will employ oral formulations of the recombinant adenovirus for the treatment of IBD in experimental animal models of the disease.
Current drug therapies for the treatment of inflammatory bowel disease (IBD) utilize corticosteroids and sulfasalazine, yet there are often severe side effects of unresponsiveness to these drug therapies. Thus, the long term objective of this proposal is to develop an alternative therapy for IBD, that is, oral formulations of recombinant adenoviral vectors containing the transgene for interleukin-1 receptor antagonist protein, or human IL-1ra. The development of successful oral adenoviral formulations would have broad applicability in the treatment of a wide variety of gastrointestinal diseases. This proposal links advances in oral delivery technology with new developments in recombinant adenoviruses, with the goal of developing a new treatment for IBD.
