www.tidewaterreview.com/features/health/sns-health-rheumatoid-arthritis-study,0,1716053.story

tidewaterreview.com

New hope for arthritis sufferers

A Northwestern University study is showing early promise for developing an effective, non-toxic treatment regimen for patients who have rheumatoid arthritis.

Ed Finkel

Special to the Tribune

March 31, 2010

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Once they're finished attacking a virus or bacteria, immune cells are supposed to die. When they instead live on, multiply in the bloodstream, and start invading and attacking joints, they cause the swelling, pain and bone destruction of rheumatoid arthritis.

Sylvia Taylor, who suffers from the disease, had to quit her job as a law firm billing coordinator in 2005, seven years after being diagnosed. Taylor has had one wrist replaced and the other fused — meaning she can no longer bend it — and she's had one foot fused.

"I'm able to walk, but I'm not able to do all the normal, physical things a person my age can do," said Taylor, 40, a mother of three who lives in Crown Point, Ind. "My range of motion isn't completely there."

A Northwestern University study is showing early promise for developing an effective, non-toxic treatment regimen for patients like Taylor.

"This occurs over time," said Harris Perlman, associate professor of medicine at Northwestern's Feinberg School of Medicine and lead researcher on the $2.25 million study funded by the National Institutes of Health. "We're trying to understand why. Not only do these (immune) cells have an increased level of longevity, but they're more toxic. So it's like a double-edged sword."

Some treatments for this disease, such as steroids and low-level chemotherapy, don't always work and are highly toxic. A newer therapy called biologic response modifiers, sometimes used in combination with steroids or chemo, works better in some patients but can cause side effects such as a greater risk of infection.

Taylor uses a medication called Rituxan that reduces her pain — and eliminates it entirely for brief periods. It has worked more effectively than other medications, although it causes a severe headache for a day or two after each dose, which she takes once every six months, and periodic nausea. "You name it, I've tried it," she said. "When you have this disease, you learn to count your blessings."

Perlman's research on mice, published in the February issue of the journal Arthritis and Rheumatism, found a lower incidence than usual of a protein called Bim, which causes immune cells to self-destruct when they're finished their jobs.

So he and his colleagues created a synthetic imitation of this protein, called the BH3 mimetic and nicknamed "Casper the Ghost," for the stealthy way in which it floats into the overactive immune cells and causes them to die when they've overstayed their welcome — or prevents them from doing so in the first place.

"We said, ‘Let's put back this protein.' How do we do it?" Perlman said. "We can create a small piece that looks and smells like the protein, attach it to ‘Casper the Ghost,' and mimic the protein. We're able to both prevent the disease and treat the disease when they have it. The best part is, we didn't see any toxicity."

In other words, other cells did not respond negatively to the drug, which meant the mice did not become ill. "That made us very excited about this process," he said. "We have a new way of targeting immune cells that promote disease development."

Perlman cautions the study is several years away from clinical trials in people. Among other steps to take before then will be developing nanotechnology so the synthetic protein can be injected into a specific joint.

"The issue we want to improve on is, how do you target and attack only the cells you want to?" he said. "This type of science is improving daily."

The study will continue with $1.8 million over five years from the National Institute of Arthritis, Musculoskeletal and Skin Diseases, and $450,000 over two years from the National Institute of Allergy and Infectious Disease, both parts of NIH.

"I'm always in support of them doing studies and finding out something new," Taylor said. "Hopefully, one day, they'll find a cure."