At age 78, Carlene Lauffer has spent more than half her life coping with the effects of two different forms of progressive arthritis. Despite her health problems, she has never let anything stop her from enjoying time with friends and family. Carlene is also an enthusiastic cook, baker and traveler. However, about 10 years ago, Carlene's hands had become so painful that it was difficult for her do many of the things she had enjoyed in the past. Joint replacement surgery alleviated her problem and gave her a unique opportunity to participate in research on an innovative therapy that may eliminate the need for surgery in the future.

Carlene has both osteoarthritis (OA) and rheumatoid arthritis (RA). OA is caused by the degeneration of the cartilage between the joints, usually due to an injury or wear and tear. In contrast, RA is an auto-immune disorder in which the joint lining swells and produces a chemical substance that attacks and destroys the joint surface. Though RA is less common than OA, it affects almost 3 million Americans. There is no cure for RA, though medications can relieve the symptoms and slow the progress of the disease. Scientists are still unsure what triggers the joint to produce chemicals that attack it.

Carlene's orthopaedic surgeon, James Herndon, MD, recommended replacing her damaged knuckles with silicon rubber implants. At the time, Dr. Herndon and Christopher Evans, MD, were studying a protein that blocks the action of Interleukin-1 (IL-1), a key substance in the inflammation and destruction of joint tissue due to RA. Drs. Herndon and Evans hoped that by finding a way to insert the gene that produces this protein into the joint, they could stimulate a response that would block the IL-1 receptors in the joint-lining. One method was to remove joint-lining cells from a patient, introduce the gene that produces the IL-1-blocking protein, and reinsert the genetically-modified cells into the joint. The joint would continue to produce the protein, essentially creating its own drug therapy.

To see if the genetically-modified cells would work and to make sure that they were safe for use in human beings, the doctors needed a patient volunteer on whom they could test the procedure. Because Carlene was scheduled to have her knuckles replaced anyway, she was a perfect candidate. On July 17, 1996, Dr. Herndon injected genetically-modified joint lining cells into two knuckles on Carlene's left hand. The other two knuckles were injected with control cells that did not contain the protein-producing gene. After Carlene's knuckles were removed, the doctors were able to compare the tissues in the two sets of knuckles to see what therapeutic effects occurred.

Carlene's joint replacement surgery made a lasting impact on her quality of life. Her pain levels declined and her mobility, flexibility and ability to use her hands all showed vast improvement after she received her prosthetic knuckles.

Carlene Lauffer was the first patient to receive gene therapy for a chronic, non-fatal disease. Since her surgery, eight other women have undergone the same procedure, and the results are still being studied. Though many more clinical trials are needed before gene therapy becomes commercially available, Drs. Herndon and Evans continue to believe in its potential for treating RA and other orthopaedic conditions. Other promising research is focusing on biological treatments and antibiotics to suppress the immune response that triggers RA in the first place. Here, too, funding will be a key ingredient to bring the research to completion.