Protein therapy may one day ease pain of rheumatoid arthritis

[Guest guest]

Protein therapy may one day ease pain of rheumatoid arthritis

Tuesday, June 29, 2004

By Shari Roan, Los Angeles Times

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 re-educate the

body, teaching it to halt its self-destructive ways.

More 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.

Source: The Los Angeles Times

Graphic: Joint affected by rheumatoid arthritis

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 the University of California, 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 percent 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 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 under way, 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.

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.