Research Teams Close In on Cause of MS : Medicine: Practical applications may be years off, but the findings could have a major impact on how the crippling disease is treated.

Two complementary research findings published in the last two days may have sharply narrowed the search for the specific types of immune cells that cause multiple sclerosis, a debilitating nerve disease that affects 250,000 people in the United States.

The discoveries, reported separately by teams from Stanford and Harvard universities, could have major implications for treating the disease. But researchers caution that it will probably be years before the findings lead to any practical therapeutic applications.

In the past, because they did not know what specific immune cells cause MS, physicians have tried to treat it by suppressing the whole immune system, a shotgun approach that has only limited effectiveness and that leaves patients susceptible to various infections.

Now, with specific immune system targets in sight, physicians may be able to suppress immune functioning much more selectively--in effect, attacking it with a scalpel rather than an ax.

“This is an interesting and very important basic immunological finding,” said Dr. Stephen Reingold, vice president of the National Multiple Sclerosis Society. But he cautioned that the results have been obtained by studying a total of only eight MS patients.

MS is a so-called autoimmune disease in which the body’s immune system attacks its own cells, specifically the myelin sheaths that encase nerves. The loss of the nerve covering, in effect, short-circuits the nerve paths, interfering with sensation and control of movements.

The course of MS is variable. Some people may have one attack and then return to a normal life. Others may have multiple attacks that cause severe degeneration. In the worst cases, MS produces complete disability.

The specific components of the immune system that attack the myelin sheath are called helper T-cells, of which there are at least 20 different families. The body makes literally millions of these cells to fight off infections but, for reasons that are not yet clear, some of them occasionally become rogue cells that attack the body. A similar process occurs in arthritis and diabetes, among other diseases.

Researchers have been searching avidly throughout the last decade for the specific helper T-cells that cause MS. Previous research uncovered two types of helper T-cells that cause an MS-like disease in mice called experimental allergic encephalitis, and that finding has made possible effective therapy in animals.

Two weeks ago, Caltech molecular biologist Leroy Hood reported that specialized, laboratory-produced antibodies, called monoclonal antibodies, designed to attack just two such T-cells could cure about 95% of mice with experimental allergic encephalitis. Researchers have hoped that if the corresponding helper T-cells could be identified in humans, effective therapy might be possible.

Now the Stanford and Harvard groups think they have made a major step in that direction.

A team of researchers headed by Dr. David Hafler and Dr. Howard Weiner of Harvard and the Brigham and Women’s Hospital in Boston report today in the journal Science that they found a specific helper T-cell in high concentrations in the blood of five MS patients, but in much lower concentrations in blood samples from healthy individuals.

A second team, headed by Dr. Lawrence Steinman of Stanford, reported Thursday in the British journal Nature that in studies of brain tissue taken from three MS patients who had died, they found at most only four types of helper T-cells, all different from the one found at Harvard. The same families of helper T-cells were not found in the brains of three people who died of other causes.

The bottom line of these observations, Hafler said in an interview, is that MS “may be more simple than we thought. We feared there could be many, many different T-cell receptors. It may be very restricted. That’s good news for patients. . . .”

Both teams were reluctant to talk about using the new findings in humans for fear of raising false hopes in patients. But Weiner and his colleagues have already used monoclonal antibodies against helper T-cells in humans in earlier studies. The improvements were modest, and the therapy had to be stopped because the antibodies--prepared in mice--caused an allergic reaction.

Hafler said Thursday that the Boston team is evaluating approaches to human therapy based on the new findings, suggesting that they may conduct human experiments with the technique fairly quickly.

Steinman said it may be two years before his group has developed the appropriate monoclonal antibodies and several more years before they can be tested in humans.