FRIDAY, Nov. 8, 2002 (HealthDayNews) -- By turning conventional wisdom on its head, researchers at Washington University in St. Louis may have identified a new drug for Crohn's disease, a chronic, lifelong disease of the gastrointestinal system.
Instead of suppressing the immune system, like most current therapies for the disease, these scientists enhanced a certain part of the immune system and saw improvement in 80 percent of the patients they studied.
"The current thinking would predict that anything that stimulates the immune system would make it worse," says Dr. Brian Dieckgraefe, first author of the study appearing in tomorrow's issue of The Lancet. "Our therapy is 180 degrees the opposite from what everybody else is doing." As he puts it, they put oil on the fire, with surprising results.
Crohn's disease affects some half a million Americans. "It's an immune response against some unknown stimulus and the inflammation [of the intestines] causes tremendous amounts of damage," Dieckgraefe says. "It's a terrible disease." It typically starts in the 20s, though children have been known to get it as well.
Kelly Perkowski, 40, a St. Louis artist and designer, developed Crohn's disease 20 years ago. "It's drastic. The symptoms are constant. You feel like you have the flu every day," she says. "There's fatigue and pain and diarrhea and abdominal pain. I can't commit to anything too far in advance or anything that is regularly occurring."
Though there are drugs for the condition, none are perfect.
"Crohn's disease is very complex, and for decades we have not been able to find an excellent therapy," says Dr. Ali Serdar Karakurum, chief of the gastroenterology division at Nassau University Medical Center in East Meadow, N.Y. "Part of the reason is we do not know the exact etiology of Crohn's disease."
Dieckgraefe and his co-author, Dr. Joshua R. Korzenik of Barnes-Jewish Hospital, decided to undertake the current study after noticing improvements in people who had genetic diseases that had Crohn's-like symptoms but weren't technically Crohn's disease.
Most strikingly, perhaps, they noticed that before 1991, when the drug granulocyte macrophage colon stimulating factor (GM-CSF), or Leukine, became available, about one-third of kids with certain genetic immune disorders developed Crohn's.
"After 1991, we couldn't identify a single kid who had developed Crohn's disease. The drug [which stimulates the immune system] may either delay its onset or block it," Dieckgraefe says.
They decided to test the drug in 15 patients with moderate to severe Crohn's disease. After receiving daily injections for eight weeks, 80 percent of the patients improved significantly, and 53 percent entered clinical remission. "That's quite impressive," Karakurum says.
Perkowski was one of those who experienced a remission. "It was amazing," she says. "I didn't feel like I had a disease. It changed my life while I was on it."
In the past, she says, different medications had caused water retention, moodiness, painful joints, bruising and more. By the time Perkowski entered the trial, she was taking 28 pills a day. During the trial, she says, "I had never felt that good. I had no side effects from the drugs."
Because they suppress the immune system, drugs such as those that are typically prescribed for Crohn's disease can be associated with life-threatening infections and can compromise the body's ability to recognize cancer cells. GM-CSF doesn't have these problems. "It is a natural protein produced in the body. It's not some unusual molecule that's been cooked up in a laboratory," Dieckgraefe says.
Since the trial ended, other scientists have identified a gene that may make people susceptible to developing Crohn's disease. The gene mutes the body's innate immune response. "It provides additional support for the idea that Crohn's disease is not an overactive immune response," Dieckgraefe adds.
Other experts are heartened by the findings as well. "It sounds like maybe a subgroup of Crohn's disease patients may benefit from this. Hopefully it's going to be an exciting approach," Karakurum says, adding that a larger, controlled trial is needed.
Dieckgraefe and Korzenik have licensed the technology to Berlex Laboratories, which has initiated a large-scale, multi-center trial. The two study authors stand to profit if the current results are borne out.
What To Do
For more information on Crohn's disease, visit the Crohn's & Colitis Foundation of America or the National Institute of Diabetes and Digestive and Kidney Diseases.
