German scientists have found evidence that gene therapy reduces symptoms in patients with rheumatoid arthritis.
The study led by an investigator at Beth Israel Deaconess Medical Center (BIDMC) was conducted on two patients with severe rheumatoid arthritis.
Originally conceived as a means of treating genetic diseases, such as cystic fibrosis and hemophilia, gene therapy involves implanting a normal gene to compensate for a defective gene in the patient.
"This study helps extend gene therapy research to nongenetic, nonlethal diseases," explained principal investigator Christopher Evans, PhD, Director of the Center for Advanced Orthopaedic Studies at BIDMC.
He added: "Rheumatoid arthritis [RA] 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.
RA is a classic autoimmune disease, which develops when, for unknown reasons, the body's immune system turns against itself, causing joints to become swollen and inflamed.
Evans had earlier identified interleukin-1 as a good target for drug therapy to cure the disease. But, he added that there was another question to deal with: How could he effectively reach the joints to block the actions of this protein?
And he found the answer in gene therapy-by implanting a gene in the affected joint, he was able to stimulate production of a human interleukin-1 receptor antagonist protein, which serves to block actions of the interleukin-1 protein.
"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 Evans.
In 2005 Evans and colleagues demonstrated that the IL-1Ra gene could be safely transferred to human joints in patients with RA.
And in the current study, the authors aimed to prove that the therapy was not only safe, but that it was of therapeutic benefit.
For the study, they recruited two subjects, both of whom were postmenopausal females under the age of 75 with a diagnosis of advanced rheumatoid arthritis.
Tissue was removed from the subjects' knuckle joints and then a harmless retrovirus was inserted into the tissue cells, in order to serve as a "vector" to transport the gene into the patients' joints.
After being placed in culture to grow and replicate, the cells were injected back into the afflicted joints.
Evans said that after four weeks, patients reported reduced pain and swelling.
"In one of the two subjects, these effects were dramatic, and the gene-treated joints remained pain-free even though other joints experience flares," he said.
Laboratory tests showed that tissues removed from the subject's joint tissue synthesized lower amounts of disease-related proteins, which confirmed that the reduction in pain and swelling was due to actions of the implanted gene.
"Existing treatments for rheumatoid arthritis are costly and need to be administered regularly. This paper provides us with the first real evidence that painful symptoms can indeed be lessened through gene therapy," said Evans, adding that in addition to risk of side effects, not all patients respond well.
Work is going on the use of gene therapy for the treatment of osteoarthritis, as well as rheumatoid arthritis.
The study is published in the upcoming issue of the journal Human Gene Therapy.