RELIEF FOR SWOLLEN JOINTS

By Christine Gorman

A killer was on the loose, and it had Lindagail Dixon, 42, of Spokane, Washington, squarely in its sights. It was her own immune system, which had gone berserk, attacking the joints in her body and crippling her so badly that she often had to use a wheelchair. Left unchecked, Dixon's disorder, rheumatoid arthritis, might have shortened her life 10 to 15 years. But last summer her doctor placed her on experimental therapy that actually wrestled her rogue immune system back into line. "I can go jogging again. I can work 10 to 12 hours on my feet," says the restaurant manager and mother of four. "It's as though I don't have the disease at all."

That's good news for the 2 million Americans who suffer from rheumatoid arthritis--not to be confused with osteoarthritis, which through normal wear and tear eventually stiffens the joints of virtually everybody who lives past age 65 or so. Rheumatoid arthritis, by contrast, is a disease of the immune system that often strikes people in their 30s and 40s, and sometimes earlier. It is a hot area of research right now because doctors believe a successful approach to rheumatoid arthritis could lead them to treatments for other immune disorders, including lupus and multiple sclerosis.

This week, at the annual meeting of the American College of Rheumatology in Orlando, Florida, scientists will announce not one but three experimental treatments for rheumatoid arthritis. Each is thoroughly modern, using genetically engineered proteins or custom-designed antibodies to combat the disease at its source, blocking the wayward steps leading to the body's self-destruction before further damage occurs.

For the past 15 years, doctors have tried to treat the underlying disorder with the pharmaceutical equivalent of a sledgehammer, using anticancer drugs and steroids to beat down the body's hyperactive defense forces. The tactic is only moderately effective and has side effects that can be as bad as the disease itself, leaving patients drained of energy and prone to sores and other infections.

What researchers now realize is that to treat the joint disease they don't have to clobber the whole immune system, just certain portions of it. Nor do they have to destroy their targets; they can merely stun them momentarily.

The three new treatments build on what scientists have learned about the ways in which rheumatoid arthritis works. The problem starts when, for reasons no one fully understands, a few misguided T cells incite other immune-system cells called macrophages to attack the joints. The approach favored by IDEC Pharmaceuticals, a biotech company in San Diego, is to target all active T cells with a custom-made antibody that can temporarily knock the immune cells out of commission. Although this antibody treatment cannot distinguish between normal and misbehaving T cells, the gambit has proved successful. More than half the 122 patients in one study showed significant improvement without debilitating side effects. "We literally had patients dancing in the halls," says Dr. Craig Wiesenhutter, director of the Coeur d'Alene Arthritis Clinic in Idaho.

Other researchers favor a more direct approach. Rather than target the T cells that get the ball rolling, they say, it's better to focus on the compounds that actually do the damage: the killer proteins produced by the macrophages. These proteins attack the cartilage and cause inflammation. One company, Immunex of Seattle, has focused on one such protein, called tumor necrosis factor. Immunex's treatment, which worked so effectively for Lindagail Dixon, consists of genetically engineered proteins that sop up excess tnf, interrupting the cycle of destruction. A third tactic, being developed by Amgen of Thousand Oaks, California, targets another inflammatory protein, interleukin-1, in much the same way. If approved by the FDA, all three drugs could be on the market in a couple of years.

Unfortunately, none of these treatments can cure the disease. When patients stop taking them, pain and stiffness return, usually in a matter of weeks or months. Nor are doctors convinced that any of these approaches will ultimately prove to be the key to conquering other immune disorders. But there's no mistaking the optimism that has taken hold among arthritis specialists. "I went for 15 years without anything new with which to treat my patients," Wiesenhutter says. "Now, all of a sudden, I have all these options."