Gene Therapy Offers Promise Against Arthritis

First human trial shows treatment safe for rheumatoid disease

WEDNESDAY, June 8, 2005 (HealthDayNews) -- For the approximately 2.1 million Americans who suffer from rheumatoid arthritis, treatment has consisted of painkillers and exercise but no cures for this degenerative joint disease.

Now the results of a phase I trial suggest that gene therapy against this common condition may be safe and feasible in humans.

"The overall direction this is moving is to develop a gene therapy for arthritis in which therapeutic genes are put into people's joints to treat the disease," said study author Christopher Evans, the Robert W. Lovett professor of orthopedic surgery at the Center for Molecular Orthopaedics at Harvard Medical School.

"We think we can come up with a treatment that is more effective, cheaper and has less side effects than existing therapies," he said.

The theory behind this treatment is that when a gene is inserted into the diseased joint, it remains there, producing a protein called human interleukin-1 receptor antagonist. This protein in turn blocks interleukin-1, which is important in the arthritis process because it inflames and destroys tissue and bone, Evans said.

"By blocking its action, we hope to reduce inflammation, decrease pain and protect the joint, so the joint remains functional," Evans said.

The findings appear in this week's issue of the Proceedings of the National Academy of Sciences.

In the trial, which was designed to determine only if gene therapy is safe, the researchers took tissue from the joints of nine women with advanced rheumatoid arthritis. They injected a harmless retrovirus in the tissues, and this virus served as a vehicle to carry human interleukin-1 receptor antagonist genes into the cells.

The cells were then injected back into the women's joints. Evans' team then compared outcomes in these joints with joints injected with untreated cells.

In earlier animal experiments, the researchers had successfully treated animals with arthritis by transferring similar genes into diseased joints. In these experiments, gene therapy was able to halt the progression of the disease and significantly reduce pain, Evans said.

"In this trial, we found that we could put a therapeutic gene into human joints and showed that the gene was fully functional," Evans said.

Evans's group found that in humans the gene transfer was successful in the treated joints. One week after treatment, the injected tissues were removed as part of already-scheduled prosthetic surgery. Evans also noted that the patients experienced no adverse side effects for up to five years after treatment.

"The next step is to do a phase II study to see if there is any clinical improvement," Evans said.

Evans sees this therapy eventually being used in the early stages of arthritis to prevent the disease from getting worse. The one treatment should last for life, he said. In addition, Evans hopes that other gene therapies will even repair damaged tissue in joints.

One expert applauded the findings.

"This study is very important, as it shows for the first time that a gene therapy approach for the treatment of rheumatoid arthritis can be conducted safely and efficiently," said Elvire Gouze, an assistant research professor in the Gene Therapy Laboratory at the Department of Orthopaedics and Rehabilitation at the University of Florida.

"This study gives a realistic optimism for the further development of gene therapy strategies for the treatment of articular [joint] disorders," Gouze added.

Another expert agreed. "The finding is really exciting," said Dr. Hayes Wilson, a rheumatologist and medical advisor to the Arthritis Foundation. "It's a neat idea to be able to put some machinery into a joint that causes the joint to make the medicine that helps the joint."

While it's too early to tell if this approach will be ultimately successful, Wilson believes the research is an important first step to achieving a novel treatment. "In the long run, this is an exciting idea," he said.

More information

The Arthritis Foundation can tell you more about rheumatoid arthritis.

SOURCES: Christopher Evans, D.Sc., Ph.D., Robert W. Lovett professor of orthopedic surgery, Center for Molecular Orthopaedics, Harvard Medical School, Boston; Elvire Gouze, Ph.D., assistant research professor, Gene Therapy Laboratory, Department of Orthopaedics and Rehabilitation, University of Florida, Gainesville; Hayes Wilson, M.D., rheumatologist, medical advisor, Arthritis Foundation, Atlanta; June 6 -10, 2005, Proceedings of the National Academy of Sciences
Consumer News