Final Activity Report Summary - IZETA_IBD2003 (Development of novel, disease-specific therapies for Crohn's disease)
The chronic inflammatory bowel disease (IBD), which encompasses Crohn's disease (CD) and ulcerative colitis is a common cause of gastrointestinal morbidity, with a combined prevalence of about 150-200 cases per 100,000 in Western Europe. Mortality from these diseases is low, but the associated problems of chronic ill health, hospital admission, drug toxicity, and surgery present an important source of morbidity. Although the aetiology of these diseases is not currently clear, epidemiological and linkage data strongly suggest that a major contributing factor for IBD is genetic susceptibility. In fact, a major advance in the understanding of IBD was found through genetic linkage analysis: the first susceptibility gene for Crohn's disease, NOD2.
However, the current challenge is to translate the scientific progress of recent years into real clinical benefit. Currently available treatments for IBD -such as azathioprine, anti-TNF-lpha agents and corticosteroids- are only effective in a proportion of patients and present toxicity problems. Clinicians and patients are eagerly awaiting the development of novel, disease-specific therapies. In this context, vasoactive intestinal peptide (VIP) has emerged as a promising candidate for treatment of Th1-driven inflammatory diseases. Moreover, its efficacy as prophylactic and therapeutic agent has recently been proven in the trinitrobenzene sulfonic acid mice model of CD. We have evaluated the efficacy of GX305, a novel formulation of VIP, as a treatment for Crohn's disease. We have performed several experiments to assess its performance in vitro and in vivo. We have also explored new ways to deliver the drug through genetic engineering of human skin cells, in order to obtain a continuous and reliable source of therapeutic peptide into the bloodstream. In fact, our main scientific achievement has been the cloning, expression and secretion of the GX305 protein from a novel source in order to improve its clinical use. Although further work is clearly needed and we still have a long way to go before its clinical use is a reality, we strongly believe that our work will enhance the quality of life of IBD sufferers in the near future.
However, the current challenge is to translate the scientific progress of recent years into real clinical benefit. Currently available treatments for IBD -such as azathioprine, anti-TNF-lpha agents and corticosteroids- are only effective in a proportion of patients and present toxicity problems. Clinicians and patients are eagerly awaiting the development of novel, disease-specific therapies. In this context, vasoactive intestinal peptide (VIP) has emerged as a promising candidate for treatment of Th1-driven inflammatory diseases. Moreover, its efficacy as prophylactic and therapeutic agent has recently been proven in the trinitrobenzene sulfonic acid mice model of CD. We have evaluated the efficacy of GX305, a novel formulation of VIP, as a treatment for Crohn's disease. We have performed several experiments to assess its performance in vitro and in vivo. We have also explored new ways to deliver the drug through genetic engineering of human skin cells, in order to obtain a continuous and reliable source of therapeutic peptide into the bloodstream. In fact, our main scientific achievement has been the cloning, expression and secretion of the GX305 protein from a novel source in order to improve its clinical use. Although further work is clearly needed and we still have a long way to go before its clinical use is a reality, we strongly believe that our work will enhance the quality of life of IBD sufferers in the near future.