Possible New Class of Drugs to Treat Osteoarthritis

Pharmaceutical researchers may soon pursue an entirely new generation of drugs to treat osteoarthritis as a result of a new study.

Researchers at the Department of Veterans Affairs led by Robert Terkeltaub, M.D., of the VA San Diego Healthcare System investigated defects in how cartilage cells “breathe” and make energy.

“Our data suggest that osteoarthritis may come to be viewed as an example of a ‘power failure’ in the mitochondria of cartilage cells,” said Dr. Terkeltaub, whose study results are published in the July issue of Arthritis and Rheumatism. Mitochondria are vital structures within the cells of the human body. Oxygen-dependent electron transport in the mitochondria helps produce energy in the cell.

Terkeltaub and his colleagues found that when this process is hampered within the cells of cartilage–the rubbery tissue between joints–osteoarthritis could develop: Healthy cartilage is not generated, calcium deposits form, and the joints deteriorate.

Little is known about the biological causes of the disease. Since osteoarthritic cartilage is chemically different from normal aged cartilage, the disease does not appear to result from aging itself. The current VA research suggests the potential for new drugs aimed at preserving mitochondrial function in cartilage cells, thereby stemming joint deterioration.

The research team found that nitric oxide, a potentially harmful free-radical gas found in the body, can significantly disturb the ability of mitochondria to consume oxygen and produce energy in chondrocytes. Nitric oxide and other free radicals are implicated as factors in several degenerative diseases.

Osteoarthritis, also known as degenerative joint disease, is the most common form of arthritis, affecting some 16 million Americans over age 60. Symptoms include pain, stiffness and inflammation in the joints. Treatments up to now have been primarily directed at symptoms and not the root cause of the disease. Treatment typically involves pain-relieving and anti-inflammatory drugs, along with heat-therapy and exercise.

Collaborating with Terkeltaub on the study were Kristen Johnson and Alexander Jung of the VA Medical Center; and Anne Murphy, Ph.D., Alexander Andreyev, Ph.D., and James Dykens, Ph.D., of Mitokor Corporation, a San Diego-based firm specializing in mitochondrial medicine.

Funding for the research was provided by the VA Medical Research Service and by the National Institutes of Health. Terkeltaub is the recipient of an Arthritis Foundation Biomedical Sciences Research Award.

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