Gene therapy promising for rheumatoid arthritis

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Researchers have successfully used gene therapy to substantially reduce joint pain in two patients with rheumatoid arthritis (RA).

These data “provide the first documented, clinical evidence that local gene therapy can provide symptomatic relief in human RA,” Dr. Christopher H. Evans and co-investigators report in the February issue of Human Gene Therapy.

RA develops when, for unknown reasons, the body’s immune system turns against itself, causing joints to become swollen and inflamed. If the disease is inadequately controlled, the tissues of the joint are eventually destroyed. There is no cure for RA, which is estimated to affect more than 2 million individuals in the U.S. alone.

"RA is an extremely painful condition affecting multiple joints throughout the body. Arthritis is a good target for (gene therapy) because the joint is a closed space into which we can inject genes,” Evans, from Harvard Medical School in Boston, noted in a written statement.

Prior studies have shown that the molecule interleukin-1 plays a key role in the breakdown of cartilage in patients with arthritis. In the current study, tissue was removed from the knuckle joints of two patients with severe RA and a harmless virus was inserted into the tissue cells, in order to serve as a “vector” to shuttle a gene that blocks action of the interleukin-1 protein to the joint. After being placed in culture to grow and replicate, the cells were injected back into the afflicted joints.

One patient who received gene therapy in two joints experienced an 85 percent reduction in pain in one joint within 1 day, and both joints were pain-free from 1 week onward. “Remarkably,” the researchers report, joints receiving the therapy were protected from flares that occurred during the study period.

The second patient also responded to gene therapy, with a 70 percent reduction in pain between weeks 2 and 3.

“Existing treatments for rheumatoid arthritis are costly and need to be administered regularly,” said Evans, adding that in addition to risk of side effects, not all patients respond well. “This paper provides us with the first real evidence that painful symptoms can indeed be lessened through gene therapy.”

Ongoing work will focus on the use of gene therapy for the treatment of osteoarthritis, by far the most common type of arthritis, as well as rheumatoid arthritis, Evans noted.

SOURCE: Human Gene Therapy, February 2009. 

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