Novel Therapy for Inflammatory Bowel Diseases: Selective Tumor Necrosis Factor-Binding Polymers

Inflammatory bowel diseases (IBDs), e.g., Crohn’s disease and ulcerative colitis, involve chronic inflammation of the digestive tract and afflict millions of people world-wide. Currently, there are no cures for IBD. Symptoms are treated with anti-inflammatory agents including corticosteroids, antibiotics, and antidiarrheals. Recently, Tumor Necrosis Factor (TNF)-binding, antibody-based drugs have been developed but these are very expensive and have the undesired side effects of weakening the immune defense and exposing patients to serious life-threatening infections. (It may also be noted that three of the four largest selling pharmaceutical products (each >$8B) are such agents: Humira, Enbrel, Remicade.)

We synthesized protein imprinted polymers (PIPs) that selectively bind the protein, TNF, i.e., synthetic polymers were created in the presence of TNF. Removal of TNF from the PIP particles produces vacant binding sites that retain 3-dimensional docking sites specific for TNF. Such PIPs should neutralize TNF activation of the inflammatory response in the GI tract. Advantages of this potential transformational therapy include: oral delivery; no systemic exposure; non-immunosuppressant; long term maintenance possible; easily administered to children (~10% of IBD patients); simpler regulatory pathway; minimal side effects.

TNF-specific cellular assays showed that PIPs selectively inhibited TNF-dependent cytotoxicity and inflammatory response in vitro, while being non-immunogenic, non-cytotoxic and non-inflammatory. We are now developing improved PIPs, to be tested in animal models and, subsequently, in human patients.

Acknowledgements: We thank the Israel Ministry of Absorption for a Grant to D. Dweck, the Hungary-Israel Bilateral Cooperation Program for support and Prof. Guenter Wulff (Dusseldorf, Germany) for wise counsel.