A Colorado State University veterinarian has been awarded a grant from the National Institutes of Health to develop a gene therapy approach to help heal cartilage and prevent osteoarthritis in horses, potentially leading to scientific methods that also may help humans.
The grant, which is $678,000 over five years, will investigate the success of treating joint injuries with a protein injected into injured joints within a virus-like agent called a viral vector.
Cartilage injuries in equine athletes are often career-ending because cartilage heals on only a limited basis. Healing is limited because a specific kind of protein or growth factor, called insulin-like growth factor, is not as available in the joint and cartilage as they are in other areas of the body. Growth factors signal the body to heal because they are responsible for a number of cellular functions, such as those that produce healthy tissue or matrix around the cells within cartilage to help heal injuries. They also trigger cells in cartilage to survive, divide and multiply.
"The lack of healing leads to cartilage degeneration and progression of osteoarthritis," said Dr. Laurie Goodrich, a veterinarian specializing in equine lameness and surgery at Colorado State University. She is also a professor in the Department of Clinical Sciences and sees equine patients in the university’s James L. Voss Veterinary Teaching Hospital. Goodrich is the principal researcher on the grant. "This prevents many horses from returning to athletic performance events."
The growth factor called insulin-like growth factor, or IGF-I, helps cartilage develop and, studies have shown, promotes healing of injured cartilage. However, researchers have not been able to develop a way to maintain enough IGF-I in an injured joint to help it heal. Goodrich and a team of researchers hope that using a viral vector to deliver DNA that increases production of IGF-I, a protein, will increase healing in damaged joint tissues.
The researchers will test the concept in a laboratory setting before beginning clinical trials on horses with joint injuries.
"While the study focuses on horses, the results may ultimately have the potential to help improve human cartilage health and reduce osteoarthritis that often follows a cartilage injury," said Goodrich. "Horses have a very similar joint anatomy, biochemical and molecular makeup as humans, and joint injuries in horses often respond very similarly as humans to treatments. This is good news for horses and humans alike as advances in joint research in horses will likely apply to humans."
The Federal Drug Administration has recently recognized that the horse is an excellent representative study model for cartilage injury and osteoarthritis in people.
Dr. Wayne McIlwraith, director of the Gail Holmes Equine Orthopaedic Research Center, and Dr. R. Jude Samulski, director of the Gene Therapy Center at the University of North Carolina, Chapel Hill, will co-mentor the project.
The project will involve collaborations with bio-informatics and gene research experts across Colorado State University, including Ken Reardon, a professor of chemical and biological engineering and Hariharan Iyers, a statistics professor. Also collaborating are Aravind Asokan, Jeff Beecham and Tal Kafri from the University of North Carolina, Dr. Alan Nixon from Cornell University, and Dr. Chisa Hidaka and Chris Chen at the Hospital for Special Surgery in New York.