Naturally Produced Enzyme May Be Useful In Inflammatory Arthritis

April 22, 1998

COLUMBUS, Ohio -- Researchers have discovered a potential method to help treat inflammatory forms of arthritis by using an enzyme naturally produced by the human body.

Researchers found that the enzyme neutral endopeptidase (NEP) could reduce some of the effects of inflammatory arthritis, according to a study in a recent issue of the journal Inflammation.

“NEP holds promise as a unique therapeutic strategy for the treatment of inflammatory arthritis,” said Patrick Ward, professor of physiology at Ohio State University and co-author of the study.

NEP works to control the levels of certain peptides, such as bradykinin, that have been linked to joint inflammation found in arthritis patients.

Peptides, short chains of amino acids, can produce inflammatory-type reactions, such as pain and increased blood flow, associated with tissue break-down. In healthy individuals, NEP is one of the enzymes which controls the effects of such peptides, Ward said.

Ward and his colleagues tested synovial fluid from the joints of three patients with rheumatoid arthritis. The researchers then added NEP to the fluid and found that NEP decreased the negative effect of the inflammatory peptide bradykinin.

While NEP could potentially be used as a drug, its high cost and the difficulty of delivery to inflamed sites would limit its use. However, Ward said that gene therapy may be a more logical solution.

“If the body is unable to manufacture enough NEP to control the inflammatory effects of these peptides, it may be possible to stimulate synovial cells to make more of their own NEP,” Ward said. He and his colleagues suggest that gene therapy may be used to insert a gene that controls NEP production.

The extra levels of the enzyme could then degrade inflammation-causing peptides and decrease damage and/or pain in joints. This concept is consistent with the broader approach of stimulating natural substances to control disease, Ward said.

“Stimulating natural substances to work at their normal sites of action has the potential to produce therapeutic actions with minimal negative side effects,” Ward said.

He added that this research was simply a feasibility study and no drug company routinely manufactures NEP yet. “If a drug company made it, the next step would be to run clinical trials that directly examine the influence of NEP in the joint. Such studies would further test the potential of NEP as a therapeutic agent for inflamed joints.”

Other researchers included Nancie Solan, Scherer Sander, Marilyn Towns and Joan Bathon, all of Johns Hopkins University School of Medicine. Grants from the National Institutes of Health and a California pharmaceutical company funded the study. Written by Holly Wagner, (614) 292-8310;

Ohio State University

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