The Secrets of Crohn's Disease

Feb. 20, 2002 -- Time was, nobody knew much about inflammatory bowel disease. That's changing fast. New knowledge is bringing new treatments.

Many of these new approaches have already reached human tests, according to an article in The New England Journal of Medicine.

Some one million Americans suffer from Crohn's disease or ulcerative colitis. These two diseases are known as inflammatory bowel disease. Both are complex illnesses.

There's not just a simple germ involved. The root cause is interplay between the environment, a person's genetic makeup, and a person's immune system.

A major clue to what's going on came with the 1996 discovery of a gene that makes some people highly vulnerable to Crohn's disease. The gene has a name -- NOD2 -- but even now, nobody's entirely sure what it does to make people sick.

Some say it plays a role in controlling the life cycle of body cells. Others say that NOD2 genes are part of the immune system's built-in seek-and-destroy germ-killing machinery. Whichever theory is correct, both offer the same kind of clue: both point to the body's relationship with intestinal flora.

Intestinal flora are the bacteria that live in everybody's gut. We've evolved along with them, so that we give them a place to grow and they help us survive. All of this is part of a delicate balance. The flora talk to the cells lining the gut, which in turn talk to the cells of the immune system. When this circuit gets broken, it upsets the balance of nature. Inflammatory bowel disease is the result.

New treatments would fix this broken circuit. All have worked in animal studies; some are now in human tests. Here are some of the new approaches:

  • Drugs that target immune cells in the mucous lining of the intestine. These are a kind of T cell that isn't getting the right message and is attacking normal cells. Slowing these guys down stops Crohn's disease in animal studies.
  • Fight T cells with T cells. This approach would teach the T cells that regulate the immune response to give the right instructions to the misguided T cells that carry out the attack orders.
  • Learn the chemical language of the gut. The right chemical signals would restore order to the inflamed bowel.
  • Drugs that would kill off the wrong kinds of bugs living in the gut without harming the good bugs.
  • Fight germs with germs. This approach would use genetically engineered "good" bacteria that would turn off harmful immune responses.