Joints swollen by arthritis? Maybe a gene fix will do.
Two patients with painful and swollen hands due to rheumatoid arthritis (RA) saw their symptoms relieved after researchers injected their knuckles with a gene that blocks a key agent of the disease.
“You basically turn the joint into a little factory that manufactures its own drugs,” said senior author Christopher Evans, the Maurice Edmond Mueller professor of orthopedic surgery at HMS and Beth Israel Deaconess Medical Center and director of the BID Center for Advanced Orthopedic Studies.
The results have yet to be confirmed in other experiments. “I believe it’s an excellent approach, but it still needs a lot of clinical studies,” said Peter Wehling, co-author of the study, published in the February Human Gene Therapy.
More than two million Americans suffer from RA, an incurable disease. For unknown reasons, the body’s defense system turns against the body, causing inflammation and pain in the joints. Although there are drugs on the market that reduce the symptoms, some patients show no improvement and suffer undesired side effects.
Evans’s approach against rheumatoid arthritis is based on gene therapy, a promising treatment that has met serious complications in some trials. It was first conceived to treat gene-related diseases such as cystic fibrosis and hemophilia. Evans’s work shows the first clinical evidence that gene therapy may work in RA, which is not a genetic disease. “You are not using the gene to compensate for a genetic defect. You are using it to deliver a gene product in a focused and selective manner,” said Evans.
The experimental treatment was a three-step process. First, researchers scooped out some tissue from the knuckles of their patients (two women under 75 who suffered advanced RA). Then they injected the therapeutic gene in a portion of the cells and let them multiply. Finally, they injected the patients’ knuckles with either modified or regular cells.
Four weeks later, inflammation receded in both patients. They also reported feeling less pain in the treated knuckles. One of the patients experienced a drastic reduction in pain and reported her joints were painless one week after the gene shot, Evans said. The second patient also saw a major reduction in pain. The gene shot was aimed at dampening interleukin-1, a main trigger for pain, inflammation and tissue destruction according to previous work by Evans. Analysis of joint tissue after the experiments confirmed low activity levels of the signaling molecule.
“This is an authentic target at least in some patients. We’ll see how many when we get further along,” Evans said. His team is now preparing a larger trial of the gene therapy technique in osteoarthritis patients. Evans also thinks his therapy may improve current treatments for RA and avoid side effects in the long run.
—Nuño Domínguez
Students may contact Christopher Evans at cevans@bidmc.harvard.edu for more information.
Conflict Disclosure: Christopher Evans is on the scientific advisory boards of Tissue Gene and Orthogen. Peter Wehling is CEO of Orthogen.
Funding Sources: The National Institutes of Health and Orthogen
