ARRA promotes development of new joint lubricant
By Susan Johnson
February 10, 2011
Gregory Jay, M.D., Ph.D.
Professor of Emergency Medicine, Medicine and Engineering, Warren Alpert Medical School of Brown University
Attending physician, Rhode Island Hospital, Providence, Rhode Island
During the championship soccer game, 21-year-old Brian made an impressive kick but landed suddenly on one leg. Grasping his knee, he rolled around in pain. In the emergency room, a doctor broke the bad news that Brian’s soccer season was over. Like more than 250,000 other people this year, Brian had torn his anterior cruciate ligament (ACL)—fibrous tissue in the knee that connects the bones of the upper and lower leg. Later, a sports medicine specialist told Brian that eventually he'd be able to play soccer again. However, in later life, this injury would make him more likely to develop a painful condition in his knee called osteoarthritis. He asked the doctor, “Can you do anything now to prevent this problem later?”
ARRA May Lead to a New Solution
Dr. Gregory Jay has often asked the same question—and he hopes to present a new solution to patients like Brian: injections of a naturally occurring joint lubricant called lubricin. With support from NIH and the American Recovery and Reinvestment Act (ARRA), Jay and other physicians at Rhode Island Hospital have been demonstrating the long-range protective benefits of lubricin after ACL injury.
Lubricin exists in joints throughout the body, helping to protect bones from wear and tear. But when a joint is injured, it loses some of this lubricant. With reduced lubrication, protective coatings on the bones—cartilage—wear away as the bones rub together. Cartilage breakdown after ACL injury or other traumas increases the risk for osteoarthritis, a chronic condition that is also more prevalent in older adults and those who are obese. The disorder is marked by painful, swollen, and stiff joints with abnormal bone growth.
Currently, there is just one approved treatment for osteoarthritis in the knee—the administration of hyaluronic acid (HA). HA thickens the protective fluid in the joint, temporarily creating a better cushion against wear. However, it is unclear whether HA prevents cartilage breakdown.
Jay, an emergency medicine specialist and biomedical engineer at Rhode Island Hospital, has been working with rats that have ACL injuries. With a well-timed grant from ARRA, he and his colleagues were able to show that lubricin helps to protect the cartilage in the rats’ knees. The intriguing question now is whether this protection also reduces the risk of developing osteoarthritis in the future. Although lubricin is not yet available commercially, these promising results are a vital step toward using lubricin to help people like Brian, who need a long-term solution and thus are unlikely to benefit from HA.
“ARRA funding was a significant supporting event,” says Jay, whose new business, Tribologics, received the funds. “Tribologics was a virtual company in the early stages of development and couldn’t have accessed commercial sources of capital. Without this support, we probably couldn't have translated our research into an animal model and laid the foundation for later human studies.”
Solving the Problem
Jay created Tribologics after he began to see potential in lubricin, but the company could not seek investment without solid evidence of lubricin’s benefits. Jay needed large amounts of research-grade human lubricin to demonstrate proof, but it would have taken him a long time and a lot of resources to create his own supply.
Over the many years that Jay and his colleagues have studied lubricin, numerous grants from NIH and other funding agencies have supported the work. However, his 2009 ARRA grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases provided a timely solution to this particular problem. With this Small Business Technology Transfer grant, Jay was able to contract with a Massachusetts company that produces biological materials.
As the patent holder and company owner, Jay has a financial stake in lubricin, and thus to avoid any appearance of bias he asked colleagues to perform all the experiments. Braden Fleming, Ph.D., an orthopedic scientist and biomedical engineer at Rhode Island Hospital, as well as a professor at the Warren Alpert Medical School of Brown University, took on this role.
Fleming’s work demonstrated lubricin’s benefits in rats; those that received a lubricin injection just after ACL injury maintained more protective cartilage in their joints. These rats also could walk more normally, a sign that they felt less pain from the injury.
“If the results are similar in humans, it’s possible that supplementing human joints with lubricin could prevent long-term knee pain,” says Jay. “More importantly, it might delay or prevent the cascade of events that lead to osteoarthritis.”
Looking to the Future
Jay, Fleming, and their colleagues have been sharing these promising results with the scientific community, through a conference presentation and papers published in 2010 and 2011. However, more studies in animals—and then trials in humans—are needed to strengthen the evidence for lubricin. After these steps are completed, lubricin could become available on the market.
“Assuming that lubricin is cost effective to manufacture, a series of human clinical studies would have to confirm that it’s safe and effective,” says Jay, explaining the path ahead. He and his colleagues are currently planning a study in larger animals to replicate their earlier results. “Depending on the regulations, human trials could take several years.”
Jay thinks that lubricin also may be useful for knee injuries in animals such as racehorses and might also work in other joints such as the shoulder.
Soccer players like Brian do not have access to this promising treatment yet. But lubricin soon may be able to help a new generation of soccer stars stay mobile and pain free later in life.
Recovery Act Investment: "Tribosupplementation of Injured Joints”; Gregory Jay; Tribologics, LLC; 2009: $207,213 (1R41AR057276-01); 2010: $77,545 (5R41AR057276-02). Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases.
Publications listing this Recovery Act Investment as providing grant support:
Jay GD, et al. Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transection. Arthritis and Rheumatism, 2010;62(8):2382-2391.
Teeple E, et al. Effects of supplemental intra-articular lubricin and hyaluronic acid on the progression of posttraumatic arthritis in the anterior cruciate ligament-deficient rat knee. American Journal of Sports Medicine, 2011; 39(1):164-172.
