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New engineered drug may offer prolonged arthritis relief

-Merck graduate dissertation fellowship.

Osteoarthritis is a degenerative joint disease that affects an estimated 21 million adults in the United States. It is the nation's most prevalent musculoskeletal disorder and the leading cause of disability, the researchers said, adding that as the average age of the population continues to rise, the incidence of osteoarthritis will increase.

Osteoarthritis had been attributed primarily to the gradual wear and tear of joint surfaces. More recently, however, scientists have discovered that inflammation sparked by the immune system also plays an important role in the worsening of the disease.

Specifically, scientists have linked a key molecule involved in inflammation, called interleukin-1 (IL-1), to osteoarthritis. IL-1 heightens the activity of enzymes that damage joints by breaking down their collagen "framework," Setton explained. She credits team member Virginia Kraus, professor of rheumatology and immunology at Duke University Medical Center, for focusing on IL-1 as a major mediator of osteoarthritis in the joint.

Given the immune system's suspected role in osteoarthritis, scientists have suspected that the interleukin-1 receptor antagonist drug, which is known to block IL-1 activity, might have value in diminishing the severity of osteoarthritis, said Mohammed Shamji, a neurosurgery resident pursuing his Ph.D. in Setton's laboratory.

However, trials of IL1RA for osteoarthritis have had limited success, primarily because the drug tends to break down quickly, according to the researchers.

"Physicians can inject large amounts of this drug systemically, but it's cleared very rapidly and there is no evidence that it reaches the joint space," said Helawe Betre, who performed these studies for his doctoral work at Duke and now works at Zimmer Orthobiologics. "We set out to develop a modified version of the drug that when injected directly might stay in the joint long enough
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Source:Duke University


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