Gene therapy for knee osteoarthritis: Q and A with Christopher H. Evans, Ph.D.

Oct. 24, 2017

Christopher H. Evans, Ph.D., is director of Mayo Clinic's Rehabilitation Medicine Research Center and associate director, translation, for Mayo Clinic's Musculoskeletal Regeneration Program.

The Musculoskeletal Gene Therapy Research Laboratory at Mayo Clinic studies joint diseases such as osteoarthritis (OA), as well as bone and tendon healing and cartilage repair after musculoskeletal injuries. Dr. Evans is the lead investigator on this study, the first in vivo gene transfer clinical trial for knee osteoarthritis in the United States.

Why is research focusing on osteoarthritis important right now?

OA affects about 27 million Americans, and the disease is a major cause of disability among older adults. OA is incurable and difficult to treat. There are few FDA-approved drugs and many patients progress to the point of needing an artificial joint.

What do past studies tell us about this vein of research and the therapeutic agent you are testing?

Recent research has highlighted the role of inflammation in the pathophysiology of OA. Our group has focused on interleukin-1 (IL-1) and emphasized its key role as an intra-articular mediator of inflammation, pain and the loss of cartilage. Its natural inhibitor, the IL-1 receptor antagonist (IL-1Ra), is thus a promising therapeutic.

We have developed a gene transfer vector (sc-rAAV2.5IL-1Ra) to deliver IL-1Ra cDNA to joints. This vector has shown efficacy in preclinical animal models, and its safety has been confirmed in a large, audited, pharmacology/toxicology study under Good Laboratory Practice (GLP) conditions.

Why does gene transfer look promising as a possible treatment for OA?

In the past, because most proteins have limited half-lives in vivo, researchers lacked the capability to deliver IL-1Ra to joints in a sustained fashion. Gene therapy allows us to do this.

Can you summarize the goals and timeline for this study?

Our primary goal is to evaluate the safety of our gene therapy for knee OA, and gain preliminary information on its possible impact on joint structure and clinical symptoms. The phase I safety study will involve nine human subjects with moderate OA of the knee who will receive an injection of the gene therapeutic in the index knee joint, in a dose-escalation manner. We will then follow these patients for one year. Production of the clinical-grade vector is underway, and we expect the team to begin enrolling and treating patients in early next year.

For more information

Mayo Clinic. A study of the safety of joint injected Sc-rAAV2.5IL-1Ra (a virus carried gene therapy) in patients with moderate knee osteoarthritis.