I have reported here previously about the advances in arthritis genetic research and the hopes that these studies would provide the basis for potential treatment options. Now researchers have reported that clinical studies show that gene therapy reduces rheumatoid arthritis (RA) patient’s symptoms.
Gene therapy was initially expected to be a method for treating genetic diseases, such as hemophilia and cystic fibrosis. Gene therapy is conducted by implanting a normal gene in order to compensate for a defective gene. The first clinical trial for testing gene therapy was initiated in 1990 to treat a rare, genetic immunodeficiency disease.
“This study helps extend gene therapy research to nongenetic, nonlethal diseases,” said lead researcher Christopher Evans, PhD, Director of the Center for Advanced Orthopaedic Studies at BIDMC. “Rheumatoid arthritis is an extremely painful condition affecting multiple joints throughout the body. Arthritis is a good target for this treatment because the joint is a closed space into which we can inject genes,” adds Evans, who is also the Maurice Muller Professor of Orthopaedic Surgery at Harvard Medical School.
Dr. Evans has been studying rheumatoid arthritis for many years and indentified interleukin-1 (IL-1) as a responsible protein in the breakdown of cartilage. The next step was to determine how to reach the joints to effectively block this protein. The answer was gene therapy.
Dr. Evans conducted follow on studies to determine the effectiveness of inserting genes into the affected joints. These studies showed that implanting an interleukin-1 receptor antagonist (IL-1Ra) protein blocked the actions of IL-1.
In one of these studies, published in the Proceeding of the National Academy of Sciences in 2005, Dr. Evans and his team showed that the IL-1Ra gene could be safely implanted into the affected joints of RA patients and that it was not only safe but also therapeutic.
[Note]“The idea is that by remaining in place, the new gene can continuously block the action of the interleukin-1 within the joints. In essence, the gene becomes its own little factory, continuously working to alleviate pain and swelling” said Dr. Evans.[/Note]
A more recent study involved two female patients in Germany with advanced RA. Tissue was removed from their knuckle joints and implanted with the IL-!Ra gene and allowed to grow and replicate in a culture. The cells were then injected back in to the affected joints.
Four weeks later the patients reported reduced pain and swelling. Further laboratory tests showed that tissues removed from the patient’s joint tissue produced less disease-related proteins, confirming that the reduction in pain and swelling resulted from the actions of the implanted gene. According to Dr. Evans, “In one of the two subjects, these effects were dramatic, and the gene-treated joints remained pain-free even though other joints experience flares.”
There will be continuing research focusing on the use of gene therapy for the treating osteoarthritis, as well as rheumatoid arthritis.