Lay Summary

Proposal No.   IBD-0108
Principal Investigator:  Britta Siegmund, M.D.
Applicant Organization:   Charité Universitätsmedizin Berlin, Campus Benjamin Franklin (Germany)
Project Title:  Specific inhibition of histone deacetylases as a novel anti-inflammatory and anti-proliferative approach in experimental colitis in mice
Period of Award:  April 1, 2004 – July 31, 2006

Inflammatory bowel disease (IBD) is associated with an increased risk of developing colon cancer.  Currently, a close endoscopic surveillance of IBD patients is required and, if precancerous cells are found, a protective colectomy has to be recommended.  Thus, the therapy of chronic inflammatory bowel disease requires the suppression of acute disease and the  maintenance of remission.  Therefore, pharmacological compounds that exert anti-inflammatory as well as malignancy-protecting properties are needed.

The group of drugs called histone deacetylase (HDAC) inhibitors includes several subgroups of pharmacological agents known to inhibit cell proliferation as well as to decrease tumor size in animal models.  Furthermore, clinical studies for solid tumors are ongoing for a variety of HDAC inhibitors.

Recently, we demonstrated that these drugs exert strong anti-inflammatory effects by downregulation of pro-inflammatory mediators.  These findings led us to propose testing the efficacy of HDAC inhibitors in experimental colitis.  In a first model of experimental colitis, disease amelioration was observed.

Thus, the proposed study aims to investigate whether treatment with inhibitors of HDAC will result in decreased inflammation and in addition will protect the animals from cancer development.  The results will contribute to the question whether this class of drugs might present a new modality for treating patients with inflammatory bowel disease.