BACKGROUND: About 500,000 people in the United States suffer with Crohn's disease. It is characterized by uncontrolled inflammation in the gastrointestinal tract. That inflammation leads to a series of complications including abdominal pain and diarrhea.
Other complications can include the development of intra-abdominal abscesses, fatigue, fever and weight loss, blood in the stool, and skin or eye irritation. The disease typically shows up in people in their late teens or early 20's.
"Most patients, at one point or another, actually will require surgery for this disease," said Brian Dieckgraefe, M.D., Ph.D., from Washington University in St. Louis.
STANDARD TREATMENTS: According to Dr. Dieckgraefe, standard therapies for Crohn's disease have attempted to suppress the immune response, but these therapies don't help everyone and there are negative side effects with many of the drugs.
"Drugs are pretty much the mainstay of therapy. The traditional mainstay of therapy is prednisone, a steroid that has very strong anti-inflammatory properties, but inherent to it, it also has some downsides," said Dr. Dieckgraefe.
Now, Dr. Dieckgraefe's research, along with co-researcher Joshua Korzenik, M.D., from Washington University, aims to offer relief to patients by stimulating the immune response instead of suppressing it.
"At first blush, this looks like we're pouring oil on a fire," Dr. Dieckgraefe said.
NEW APPROACH -- NEW THERAPY: Dr. Dieckgraefe and Dr. Korzenik found several genetic disorders characterized by an impaired immune system also were associated with Crohn's-like gastrointestinal problems. Patients with genetic immune system disorders are often treated with drugs that stimulate the body's immune response.
One of those drugs is a recombinant version of a protein that the body produces to enhance the immune response. It does this by increasing the number and function of white blood cells. The drug, dubbed GM-CSF, which stands for granulocyte-macrophage colony stimulating factor, is also known by the brand name, Leukine. The drug stimulates the immune system and is administered by daily injection.
In an initial study of 15 people with Crohn's disease, researchers found 80 percent of them improved significantly with the drug and 53 percent were considered to be in remission. They also found when treatment with the drug stopped, symptoms tended to return. When therapy was started again, symptoms cleared.
FUTURE: The drug is already FDA approved for other conditions, but larger trials need to be conducted before it can be prescribed for Crohn's disease. Researchers are now involved in a larger, multi-center phase II trial taking place at about 30 sites across the country. The trial will enroll 120 patients. Dr. Dieckgraefe says he is optimistic about the future of this treatment for Crohn's disease.
"This is a new approach to treatment that may not have the associated downside of the potent immunosuppresant medication. I think this is going to launch a series of investigations that will allow us to better understand what the genetic deficiencies are in individuals with Crohn's disease and allow this and other therapies to more directly target that defect," Dr. Dieckgraefe said.
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