DoD grant supports preclinical tests of osteoarthritis gene therapy

Researchers at Baylor College of Medicine have been awarded a Technology/Therapeutic Development Award for more than $5 million over four years from the Department of Defense Congressionally Directed Medical Research Programs to support late-stage preclinical testing of a viral gene therapy treatment for osteoarthritis. The award is focused on catalyzing innovative therapies into the commercial development.

“Osteoarthritis is one of the most common diseases in the population. Everyone will get it if they live long enough, and there’s no FDA-approved disease modifying therapy other than joint replacement,” said Dr. Brendan Lee, principal investigator of the study, professor and chair of the Department of Molecular and Human Genetics and Robert and Janice McNair Endowed Chair and Professor in Molecular and Human Genetics at Baylor. “There’s an enormous unmet need in therapeutics, so we’re excited to move this gene therapy forward.”

Previous work at Baylor led to the development of the first gene therapy using a helper-dependent adenovirus vector and successful in vivo testing in mouse and horse models of osteoarthritis. The therapy leads to long-term expression of the IL-1RA protein, which blocks inflammation in the joints, but unlike other similar approaches, this treatment activates the protein expression only when inflammation is present in the joint. This may be important as inflammation can have both negative and positive effects. As a result, the gene therapy approach was licensed to the German biotech company GeneQuine Biotherapeutics. GeneQuine developed the therapy further and later sold it to Flexion Therapeutics, which was acquired by Pacira Biosciences in 2021. The therapy, PCRX201, is currently in Phase 1 clinical development.

This technology also is the basis for a combination therapy approach using a vector that expresses both IL-1RA and a protein called lubricin, which is the subject of this new study, a collaboration between GeneQuine, Baylor and Cornell University College of Veterinary Medicine. Earlier studies in the Lee laboratory have shown the combination therapy leads to a greater effect than single therapy of either protein in mouse models. Baylor researchers will compare the combination therapy delivered in a single virus to therapies expressing IL-1RA and lubricin alone in both mouse and horse models of osteoarthritis.

“With osteoarthritis, it’s unlikely a single monotherapy will be sufficient for optimal treatment because a complex disease requires combination therapies,” Lee said.

Researchers hope this treatment will preserve joint cartilage, maintain gait and mobility and decrease pain. According to Lee, viral gene therapy could eventually be used to delay progression of osteoarthritis or to treat joint injuries.

“When there’s an injury to a joint, even if it’s repaired with surgery or physical therapy, you’re at a dramatically increased risk for developing osteoarthritis later in life,” Lee said. “We hope this therapy could be delivered after an injury to delay the effects of osteoarthritis.”

The Lee laboratory is collaborating with GeneQuine and Pacira Biosciences in advancing this treatment to clinical trial.
Lee also is director of the Center for Skeletal Medicine and Biology and managing director of the Lawrence Family Bone Disease Program of Texas.