Diseases in which the body attacks its own tissue are among the most difficult to understand and treat. But in the case of one such disorder, rheumatoid arthritis, researchers may eventually be able to reeducate the body, teaching it to halt its self-destructive ways.
The therapy, called immune modulation, could ease the pain of 2.1 million Americans affected by the joint condition.
"Inflammation is like a fire that destroys the joint," Dr. Salvatore Albani, a professor of medicine and pediatrics at UC San Diego, says of the immune reaction. "We are trying to address the mechanisms that generate inflammation."
Normally, such a reaction is caused by the body's recognition of a foreign invader, such as bacteria, and its attempts to oust the alien. But sometimes, for reasons that are still mysterious, the body turns its immune response on its own tissue, resulting in an autoimmune disorder, a category that includes lupus and scleroderma.
Traditionally, people with rheumatoid arthritis have been treated with painkillers to relieve symptoms. More recent medications, such as Enbrel, have suppressed part of the immune response. But those therapies can have serious side effects and increase the risk of infection. Immune modulation targets the cause of the wayward immune response.
In a recent study, Albani and his colleagues demonstrated that a synthetic peptide -- a chain of amino acids -- in the form of a tablet, appears to disrupt the immune response in people with rheumatoid arthritis without causing side effects.
"We're getting to a level of treatment that is more sophisticated: figuring out what triggers the autoimmune response in these patients and going after that," says Dr. Joan Merrill, head of clinical pharmacology at the Oklahoma Medical Research Foundation. "If you could just figure out how to turn off the immune response to this thing -- without affecting the body's ability to fight off viruses and bacteria -- that would be so much more clever and strategic."
Albani's work, published recently in the Proceedings of the National Academy of Sciences, takes this approach, Merrill says.
In earlier work, Albani and colleague Dennis Carson had found that the immune system in rheumatoid arthritis becomes confused by a sequence of amino acids, called a human leukocyte antigen, produced on the surface of cells during an immune response. About 70% of rheumatoid arthritis patients -- but not healthy people -- share a specific sequence of amino acids within that antigen.
In a normal immune response, a human leukocyte antigen acts like a dimmer switch to prevent an excessive inflammatory response; that dimmer is broken in people with rheumatoid arthritis, Albani says.
To prevent an excessive response, Albani focused on a naturally occurring protein, dnaJ, that the body uses body to help initiate inflammation. A section of the dnaJ protein, dnaJP1, contains the same unusual sequence of amino acids as those found in rheumatoid arthritis patients.
Albani theorized that by administering a synthetic version of the dnaJP1 protein to patients by mouth, he could reeducate the body to recognize and tolerate this specific amino acid chain instead of seeing it as an invader.
"It's like a vaccine, in broad terms, meaning that it reeducates the immune system," he says.
A key to the therapy is delivering the drug by mouth, says Albani, because the stomach is the one area of the body that doesn't react harshly to foreign invaders, such as food. In his previous study, Albani used blood tests from 15 patients to demonstrate that the therapy had successfully manipulated the immune response to behave normally instead of in an aggressive manner. The study was not designed to assess patients' symptoms.
In a new study underway, researchers at eight medical centers are testing the peptide in 160 people in a randomized trial. Patients will receive either the peptide or a placebo and will undergo blood tests and evaluation of their symptoms. The study, scheduled for completion later this year, is financed by the National Institutes of Health.
"People wonder, how can such a small quantity of a peptide, taken by mouth, have such an effect on the immune system," Albani says.
The research is promising enough to generate excitement, however, Merrill says. "They have shown they can move the immune response away from the classic kind of hyperactivity you see in rheumatoid arthritis," she says.
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About rheumatoid arthritis
* The lining of joints or internal organs becomes inflamed. Typically, many joints are affected.
* The condition is typically chronic, characterized by periodic flare-ups.
* Symptoms include pain, stiffness, redness, warmth and swelling in the joints.
* The inflammation can invade and damage bone and cartilage.
* The cause is unknown. Some researchers suspect viruses may trigger rheumatoid arthritis in people who have an inherited tendency for the disease.
* The problem is far more common in women. It often first occurs in middle age, but children and young adults can also be affected.