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New Treatment Strategy For Crohn's Disease Shows Early Promise

Date:
November 11, 2002
Source:
Washington University School Of Medicine
Summary:
A preliminary study reports that enhancing the body's innate immunity can improve symptoms of Crohn's disease in 80 percent of patients with moderate to severe forms of the debilitating, inflammatory gastrointestinal disorder.

A preliminary study reports that enhancing the body's innate immunity can improve symptoms of Crohn's disease in 80 percent of patients with moderate to severe forms of the debilitating, inflammatory gastrointestinal disorder.

The results are reported in the Nov. 9, 2002 issue of The Lancet by investigators at Washington University School of Medicine in St. Louis.

Crohn's disease is a chronic, lifelong condition, which affects about half a million people in the United States, according to co-principal investigator Brian K. Dieckgraefe, M.D., Ph.D., assistant professor of medicine in the Division of Gastroenterology at the School of Medicine and staff physician at Barnes-Jewish Hospital.

"It usually begins between the ages of 20 and 30, and a typical patient deals with diarrhea, abdominal pain, infections and very serious problems that require surgery," Dieckgraefe says. "It's just a terrible situation."

Until now, the disease has been thought to result from an overactive immune system, and therapies have attempted to suppress, rather than enhance, the immune response. Therapies that suppress immunity improve symptoms in many Crohn's disease patients, but researchers are looking for alternative treatments to help those who don't respond. Most of that work, however, involves finding pathways to suppress immunity.

"At first blush, the idea of priming the immune system in patients with Crohn's disease sounds sort of like throwing oil on a fire," says co-principal investigator Joshua R. Korzenik, M.D., assistant professor of medicine in the Division of Gastroenterology and staff physician at Barnes-Jewish Hospital. "You might compare it to proposing a high cholesterol diet to treat heart disease."

But the team's research the past few years suggests that Crohn's patients may benefit from this alternative treatment approach. Korzenik and Dieckgraefe found that several genetic disorders characterized by an impaired immune system also were associated with Crohn's-like gastrointestinal problems.

They looked at two disorders in particular. About one-third of patients with glycogen storage disease 1B -- which causes abnormal glucose metabolism -- also had Crohn's disease symptoms. They found the same thing in patients with the genetic disorder chronic granulomatous disease.

Patients with these and other genetic immune system disorders often are treated with drugs that stimulate the body's immune response. One such drug is a recombinant version of a protein produced by the body to enhance the immune response by increasing the number and function of white blood cells. Granulocyte-macrophage colony stimulating factor (GM-CSF), also known by the trade name Leukineฎ (sagramostim), not only assists with the primary symptoms of these immune disorders, but also helps eliminate Crohn's disease symptoms.

Another distinction between this treatment and traditional Crohn's therapies is that GM-CSF targets the innate immune response -- the body's built-in defense against infectious organisms. Most current Crohn's disease treatments interfere with what's called acquired immunity, which develops over time as the body encounters new infections. Generally, the innate immune system attacks infectious agents first, holding down the fort until the acquired immune system can take over.

Because of the link between immune system disorders and Crohn's disease, and because of the connection between treatment with GM-CSF and recovery from Crohn's-like symptoms, Dieckgraefe and Korzenik tested the drug in 15 patients with moderate to severe Crohn's disease.

"Conventional thinking would have predicted that these drugs could worsen the disease," Dieckgraefe says. "But we thought that these immune deficiencies provided a good model for how our Crohn's patients would respond. Furthermore, we knew that GM-CSF was a natural protein that already was present in the body."

Patients received daily injections of GM-CSF for eight weeks. They were evaluated during the study both for the severity of their disease -- using a tool called the Crohn's disease activity index (CDAI) -- and their quality of life -- using the Inflammatory Bowel Disease Questionnaire (IBDQ).

Of the 15 patients who received GM-CSF, 12 (80 percent) improved significantly during the study, and eight (53 percent) were considered to be in clinical remission following treatment. The average CDAI score fell by 190 points, indicating a significant decrease in Crohn's disease symptoms. The average IBDQ score increased from 108 to 179, indicating significant improvements in quality of life.

The researchers have continued to follow many of the 15 study patients, and they have found that when treatment with GM-CSF stops, symptoms tend to return. But when treatment resumes, symptoms again improve.

"The results of this open-label trial make us optimistic that this approach may someday help large numbers of patients who don't respond to traditional Crohn's disease therapy," says Korzenik. "However, we need to test our findings in a larger, randomized, placebo-controlled trial."

Based on these preliminary results, Berlex Laboratories Inc. -- the pharmaceutical firm that owns Leukine -- has initiated a large-scale, multi-center study to see if these findings can be replicated.

Reference: Dieckgraefe BK, Korzenik JR. Treatment of active Crohn's disease with recombinant human granulocyte-macrophage colony-stimulating factor. The Lancet, vol. 360, pp. 1478-1481, Nov. 9, 2002.

This research was supported by a General Clinical Research Center grant from the National Institutes of Health. Yeast-derived recombinant human GM-CSF and financial support were provided by the Immunex Corporation. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation or the writing of the report.



Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "New Treatment Strategy For Crohn's Disease Shows Early Promise." ScienceDaily. ScienceDaily, 11 November 2002. <www.sciencedaily.com/releases/2002/11/021111070012.htm>.
Washington University School Of Medicine. (2002, November 11). New Treatment Strategy For Crohn's Disease Shows Early Promise. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2002/11/021111070012.htm
Washington University School Of Medicine. "New Treatment Strategy For Crohn's Disease Shows Early Promise." ScienceDaily. www.sciencedaily.com/releases/2002/11/021111070012.htm (accessed August 28, 2014).

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