Novel Anti-inflammmatory Antibody Therapy for Inflammatory Bowel Disease

Abstract Inflammatory Bowel Disease IBD including primarily Crohnandapos s disease CD and ulcerative colitis UC is a chronic debilitating condition with no effective treatment The economic impact is disproportionally high because it affects primarily young individuals years old and the characteristic periods of remission and relapse necessitate frequent hospitalizations Furthermore some of patients with total bowel involvement will have colectomy and of patients with CD require some type of surgical intervention during their lifetime Symptoms like bloody diarrhea abdominal pain general malaise and fever significantly compromise quality of life IBD affects million Americans with annual healthcare costs approaching $ billion Current therapies anti inflammatory drugs immunosuppressants antibiotics and drugs for symptomatic relief are only modestly effective and often cause unacceptable adverse events particularly with long term use A new generation of biologics targets pathways of immune activation to block proinflammatory signaling All seven biologics showing clinical benefits in IBD are monoclonal antibodies including TNF integrin and IL blockers Mucosal healing and long term remission occur in only a minority of patients Significantly rare but life threatening conditions including increased risk for serious infections non Hodgkinandapos s lymphoma and melanoma have been associated with chronic exposure to anti TNF therapies The pharmaceutical management of IBD despite the revolutionizing use of biological therapies remains problematic Recent data support the hypothesis that melanin concentrating hormone MCH is a crucial link in inflammatory events affecting the mucosa Results from four animal models support a pivotal role for MCH signaling in IBD Both MCH and MCH receptor MCHR expression levels are elevated in biopsies of inflamed mucosa from IBD patients relative to non involved mucosa from the same patients A polyclonal rabbit anti MCH antibody attenuates chronic colitis and fibrosis in two animal models of colitis Further supporting a role for MCH in IBD MCH knock out mice are protected from experimental colitis induced by trinitrobenzene sulfonic acid TNBS During this Phase I project we will identify and characterize a neutralizing anti MCH human monoclonal antibody humAb Evaluation in both in vitro cellular and in vivo rodent models will be carried out We are optimistic that this work will result in a new therapeutic for CD and UC This biological therapy will reduce inflammation fibrosis and prolong periods of remission among patients suffering from IBD Narrative Inflammatory bowel disease IBD involves chronic inflammation of all or part of the colon IBD can be painful and debilitating necessitating frequent surgeries in many cases and sometimes leads to life threatening complications Current treatments are only modestly effective We have developed a new therapeutic that has the potential to reduce inflammation and tissue damage in this intractable disease