THURSDAY, Sept. 26, 2002 (HealthDayNews) -- In a scientific and medical breakthrough story that might have come out of a Hollywood script, researchers say they have discovered the cause of the autoimmune disease celiac sprue and are on the track toward a treatment for it.
Reporting in tomorrow's issue of Science, a group led by Chaitan Khosla, professor of chemistry and chemical engineering at Stanford University, says it has identified the specific protein fragment that causes a destructive attack on the intestinal tract when people with celiac sprue eat grains such as wheat, rye, and barley.
The researchers also report finding an enzyme that can attack that protein and that might someday be used to treat the condition.
People with celiac sprue have a genetically based inability to digest gluten, a major protein component of grains. The only effective therapy is to avoid all gluten-containing products, a daunting dietetic challenge. When gluten is ingested, immune cells attack the lining of the intestinal tract, causing digestive difficulties and increasing the risk of cancer. One of every 2,000 or 2,500 Americans has been diagnosed with celiac sprue, but the actual incidence is believed to be one in 200, with many people unaware that they have the condition.
One of those people was Khosla's wife. As he explains it, she had some early childhood problems, but then the symptoms became too vague and diffuse to diagnose. It was only when their son became very sick and was diagnosed that she was tested and found to have the disease.
"A week after she was diagnosed, I was sitting in my office trying to make sense of it, when I got a call from the head of the National Science Foundation," Khosla says. "I had been given an Alan T. Waterman award, a very generous grant to do anything I wanted. To me the answer was simple, to educate myself about the cause of celiac sprue."
Khosla put a graduate student, Lu Shan, to work in the laboratory, exposing gluten to digestive enzymes. The work was "in concept quite straightforward but technically very challenging," says Khosla. By what he describes as "good sleuthing on the part of Lu Shan," she was able to identify a protein fragment of gluten, made up of 33 amino acids, that was broken down by the digestive process in disease-free individuals but not in those with celiac sprue. She is listed as the lead author of the journal report.
Tests using cells from persons with celiac sprue showed that this fragment caused the damaging attack by immune system T cells in the intestine, Khosla says. The obvious next step was to find an enzyme that could break down the protein fragment. The researchers have found such an enzyme and have tested it successfully in cell cultures and animals, but Khosla warns against undue optimism.
"Our work has just started," he says. "It is a mistake to raise false hopes. We will do the best we can and not give up until we get there."
"There" is an enzyme that could be taken to allow persons with celiac sprue to digest gluten-containing products, in the same way that the enzyme lactase allows persons with lactose intolerance to drink milk. But years of animal tests are needed before any human trials can begin, and it's not certain that the newly identified enzyme will be the answer.
"In the next couple of years we will ask if the hypothesis that it might detoxify gluten will work," he says. "If the answer is yes, we will go on to human tests. But we might think of a better enzyme. This one is not a magic bullet."
Khosla is establishing the Celiac Sprue Research Foundation to finance that work. It will be looking for donations from individuals, he says, with the hope of establishing a partnership with a pharmaceutical company.
This is "an important finding," says Dr. Martin F. Kagnoff, director of the laboratory of mucosal immunology at the University of California at San Diego and a spokesman for the Celiac Sprue Association. "It is certainly a step forward, and whether or not it will lead to new therapies, it certainly gives insight into ways to treat the condition."
The finding does not solve a major genetic mystery about celiac sprue, Kagnoff says. The condition has been related to an immune system molecule, but "for every 100 people who have the molecule, only two get the disease, so other genes or environmental factors play a role," he says. "Still, this is a key finding in understanding how the immune injury takes place."
What To Do
You can get more information about celiac sprue from the Celiac Sprue Association, the National Institute of Diabetes and Digestive and Kidney Diseases, or Khosla's new organization, the Celiac Sprue Research Foundation.
