Crohn’s disease is one of a group of conditions called inflammatory bowel diseases. As many as 1 million Americans suffer from these conditions, which are often disabling. The cause of these diseases is not known, but they involve inflammation or irritation of the digestive tract, and scientists think the body’s own immune system may be the culprit. Crohn’s disease can affect any part of the digestive tract and causes abdominal pain, severe diarrhea, ulcers and sometimes malnutrition because it reduces the body’s ability to absorb nutrients from food. No cure is known, but symptoms can be relieved in some cases by drugs that reduce inflammation or suppress the body’s immune system. Because the growth of new blood vessels, called angiogenesis, may be necessary for the inflammation to proceed, the researchers are developing a treatment for Crohn’s disease that acts by blocking angiogenesis, which may decrease inflammation in the intestines.
Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are chronic inflammatory disorders of the intestinal tract that are currently believed to arise from a complex interaction among the environment, the immune system and the genetic make-up of affected individuals. Recent studies of patients with active IBD have pointed out an increased vascularization in the inflamed mucosa, suggesting that stimulation of angiogenesis may play an important pathophysiological role in establishing and sustaining tissue inflammation, therefore playing an integral role in IBD pathogenesis. We have utilized two spontaneous models of Crohn’s disease to evaluate the therapeutic potential of a novel anti-antigenic peptide, ATN-161, that is currently being evaluated in phase II trials in cancer patients. ATN-161 binds to a number of β integrin–containing heterodimers implicated in angiogenesis, including ±vβ3 and ±5β1, and has demonstrated antiangiogenic activity in a number of preclinical studies. ATN-161 had significant therapeutic activity when used in both of the models of Crohn’s disease in which it was tested, decreasing both histological indices of intestinal inflammation and clinical scores of disease activity.
We believe that these data, combined with the benign adverse event profile observed in 28-day repeat dose non-clinical toxicology studies and the phase I trial in advanced cancer patients, provide a solid rationale for the development of ATN-161 for the treatment of Crohn’s disease.
Case Western Reserve University, Cleveland
Jeffry Katz, M.D.
Public Health Impact
A phase I trial of ATN-161 for the treatment of Crohn’s disease would be the very first strictly anti-angiogenic intervention used in this condition and would test the hypothesis that angiogenesis is required for the maintenance of Crohn’s disease.
Work on this project is complete.
- Formulation development
- Pharmacokinetic/absorption, distribution, metabolism, and excretion (PK/ADME) studies