NIH Awards $7.5M, Designates URMC Orthopaedics as Center of Research Translation

Aug. 30, 2012
Regis O'Keefe, M.D., Ph.D.

The University of Rochester Medical Center was granted a $7.5 million Center of Research Translation (CORT) award for programs designed to find new therapies for arthritis and bone healing. With a rising population of older adults, musculoskeletal diseases are a major economic burden in the United States and in the health-care system, and the award places the URMC in a leadership role for seeking solutions.

“This was an extremely competitive process. The CORT award is a major achievement for the Medical Center and our programs in musculoskeletal research and patient care,” said Mark B. Taubman, M.D., Dean of the School of Medicine and Dentistry. “It will enable our continued focus on innovations that can improve patient care and the health of our community and other communities across the country.”

Regis O’Keefe, M.D., Ph.D., the Marjorie Strong Wehle Professor in Orthopaedics and department chair, is the principal investigator. He noted that the unique structure of CORT requires collaboration among scientists, and rewards institutions that build on previous work in a highly integrated environment.

“The best approach to solving challenging scientific problems is when teams of investigators bring different skills and perspectives, and a different understanding of an array of technologies and methods,” O’Keefe said. “It’s the knowledge of the entire group and not just one individual that produces results.”

The five-year grant begins Sept. 1. Scientists will primarily investigate the regulation of stem cells in joint tissue and bone, and how tissues respond after musculoskeletal injury to knees and hips. Much of their work will involve parathyroid hormone (PTH), an essential ingredient in the drug Forteo.

The Food and Drug Administration has approved Forteo to treat osteoporosis. However, based on strong preliminary data, URMC orthopaedics researchers believe they can demonstrate that PTH also builds cartilage around joints and has the capacity to activate stem cells for healing degenerating joint tissues and bone fractures.  If so, the research into PTH could yield new therapies for the millions more patients who have osteoarthritis (OA) instead of, or in addition to, osteoporosis.

The CORT grant funds three key initiatives:

1.      The investigation of Forteo as a treatment for osteoarthritis following traumatic knee injury. Led by Michael J. Zuscik, Ph.D., associate professor in the Department of Orthopaedics, this series of studies determine the pathways and protein receptors involved in PTH’s ability to preserve articular cartilage and to stimulate healing of articular cartilage. If successful, the work provides a rationale for using parathyroid hormone as a treatment to for osteoarthritis and to prevent joint damage following knee injury.

2.      Investigating the role of PTH in fracture repair in the context of aging, which delays the healing of connective tissues. Led by O’Keefe, this project is designed to show how PTH acts specifically on mesenchymal stem cells (which give rise to cartilage, bone, and connective tissues), to more quickly stimulate the formation of new bone and healing tissues. This project attempts to address the prevalence and disability associated with hip fractures, which is among the top three Medicare costs to hospitals, O’Keefe said.

3.      Translating how PTH therapy can improve the healing of major bone defects caused by trauma. Led by Edward M. Schwarz, Ph.D., the Burton Professor of Orthopaedics and director of the URMC Center for Musculoskeletal Research, investigators are studying the role of PTH in preventing the body’s negative reaction to reconstructive surgery following trauma or cancer.

The CORT grant is an extension of an initial funding period, which began in 2006 under Randy N. Rosier, M.D., Ph.D., professor of Orthopaedics, and a leader at the URMC Clinical and Translational Science Institute. By funding the renewal, the National Institute of Arthritis and Musculoskeletal and Skin Diseases noted significant progress, which positions URMC to exert a powerful influence over the pursuit of new therapies for OA.

Despite having a low mortality rate, musculoskeletal diseases impact more Americans than any other health condition in terms of loss of independence, work capacity, and quality of life, according to the U.S. Bone and Joint Initiative. Osteoarthritis in particular afflicts an estimated 27 million Americans, compared to about 1.3 million for rheumatoid arthritis. There is no cure for OA, and treatment usually focuses on relieving pain and improving joint function.

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