Crohn's Disease (Colitis)

Crohn’s disease and ulcerative colitis, which affect approximately a million people in the United States, are fundamentally diseases of inflammation. Those suffering from the disease display excessive inflammation in the lining of the small intestine, which leads to abdominal pain, diarrhea, and, in some cases, bleeding that can cause anemia. Typical treatments aim to reduce inflammation, and severe cases may require surgery. No treatment at this time, however, constitutes a cure—the condition returns even in those patients who undergo surgery. Furthermore, all currently available treatments have associated side effects such as nausea, heartburn and increased susceptibility to infections. Additional research is needed in order to develop more effective treatments.

Sanford-Burnham research on Crohn's disease

Professor Hudson Freeze and his colleagues at Sanford-Burnham are examining inflammation at the level of individual cells and molecules that mediate the process. They hope their work will lay the foundation for a new generation of treatments for inflammatory diseases.

The team recently produced an antibody that blocks inflammatory intestinal conditions in animal models. Mice given a control antibody, or placebo, lost approximately a quarter of their body weight and suffered from severe diarrhea. But mice treated with Dr. Freeze’s antibody showed minimal weight loss (less than 10%), were healthy and had no signs of diarrhea. The antibody inactivates a group of novel sugar chains the laboratory had identified as important in fueling various types of inflammation. Sugar chains are found attached to many of the proteins that carry out the body’s functions and they often modify those functions. The sugar chains discovered by the Freeze group are found on proteins and cells of the immune system known to play a key role in inflammation.

Inflammation is a critical bodily process that helps to protect us from infection, but when it goes awry and attacks our own tissues, as in Crohn’s and other conditions such as arthritis, it must be reined in. This is the aim of many current therapies, such as corticosteroid drugs, which damp down the immune system. An unfortunate side effect of such treatment, however, is to compromise the body’s ability to ward off infections. A promising aspect of the Freeze antibody is that it appears to affect cells of the immune system specifically in the intestinal lining and not in critical tissues such as the lung.

Dr. Freeze and his group continue working to pinpoint the underlying mechanism of the antibody’s action and determine what other types of inflammation may be treatable with it.

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