Mayo researchers prepare to launch clinical trial using gene therapy for knee osteoarthritis

Oct. 26, 2016

A Mayo research team led by Christopher H. Evans, Ph.D., plans to use a viral vector to introduce an anti-arthritic gene into the knee joints of patients with osteoarthritis (OA). Dr. Evans is director of Mayo Clinic's Rehabilitation Medicine Research Center and associate director, translation, for Mayo Clinic's Musculoskeletal Regeneration Program. Funded by a Department of Defense grant, the study's primary goals are to evaluate the safety of gene therapy for knee OA, as well as the treatment's possible effects on joint structure and clinical efficacy.

Approximately 27 million Americans have OA, and the disease is incurable, largely untreatable and the major cause of disability among older adults. Earlier research has established that interleukin-1 (IL-1) is a key intra-articular mediator of the pathophysiology of OA, and that its natural inhibitor, the IL-1 receptor antagonist (IL-1Ra), is a promising therapeutic.

"Using traditional technology, IL-1Ra is impossible to deliver to joints in a sustained fashion," says Dr. Evans. "Gene delivery is a solution to this problem."

The team has developed a recombinant adeno-associated virus (AAV) carrying the IL-1Ra cDNA (sc-rAAV2.5IL-1Ra) as a therapeutic for injection into joints with OA. “The efficacy of this agent has been shown in preclinical animal models, and its safety has recently been confirmed in a large, audited, pharmacology/toxicology study under Good Laboratory Practice (GLP) conditions," says Dr. Evans.

The team plans to conduct a Phase I safety study in nine human subjects with moderate OA of the knee. The gene therapeutic will be injected into the index knee joint of nine patients with OA of the knee in a dose-escalation manner, and the patients will be followed for one year.

The research team also hopes to study these secondary outcomes:

  • Expression of IL-1Ra in synovial fluid and serum
  • Possible presence of viral genomes in peripheral blood
  • Possible humoral or cell-mediated immune responses to the viral vector and IL-1Ra
  • Possible effect on joint structure, as determined by MRI
  • Possible clinical efficacy, as determined by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and pain scores

Right now, the team is awaiting the manufacture of clinical-grade vector. Once the vector is delivered, Dr. Evans expects the team to enroll and treat patients in early 2017.

The Musculoskeletal Regeneration Program is based at Mayo Clinic's campus in Rochester, Minnesota. Physicians and scientists in this new program are focused on the repair of diseased or injured tendons, ligaments, cartilage, muscle and bone using advanced stem cell and tissue engineering platforms. This work involves a multidisciplinary team encompassing orthopedic surgery, sports medicine, physical medicine and rehabilitation, and rheumatology, with the common goal to improve the current standard of care. These emerging regenerative technologies, focusing on structural repair and functional restoration, are poised to provide innovative solutions that address unmet patient needs. In separate studies, Mayo researchers are using gene therapy to regenerate cartilage and heal bone.