Intra-articular Recombinant Lubricin to Restore Joint Lubrication and Prevent Osteoarthritis in Horses
Principal Investigator: Heidi L. Reesink
DESCRIPTION (provided by applicant):
The long-term objective of this research is to translate lubricin therapy to equine clinical patients. Although results have been promising in rodent and mini pig models, recombinant lubricin therapy has yet to be tested in horses. This is, in part, due to technical challenges associated with producing sufficient quantities of recombinant lubricin for a large animal trial and also due to competing demands for testing recombinant lubricin in human clinical trials. Because our #1 priority is making this therapy available to horses, the objective of this proposal is to test intra-articular recombinant lubricin therapy in an equine model. Our experimental approach utilizes IL-1ß-induced synovitis to study how joint inflammation, common to racehorses, affects synovial fluid lubrication. This model is ideal for evaluating biochemical and mechanical synovial fluid parameters in addition to clinically relevant lameness outcome measures, in response to intra-articular recombinant lubricin therapy.
Specific Aim 1. To investigate how synovitis affects equine synovial fluid inflammatory profiles, lubricating parameters and lameness. In Aim 1, we will evaluate how inflammatory cytokines, lubricants (lubricin and hyaluronic acid) and joint lubrication are altered in equine IL-1ß-induced synovitis. We will assess how these biochemical and lubrication parameters correlate with clinically relevant outcome measures, such as lameness, prior to evaluating the ability of recombinant lubricin to ameliorate inflammation and restore joint lubrication in this model.
Specific Aim 2. To assess the ability of intra-articular recombinant lubricin to a) mitigate inflammation, b) enhance synovial fluid lubrication and c) reduce clinical measures of lameness following IL-1ß-induced synovitis. In Aim 2, we will evaluate the ability of intra-articular injections of recombinant lubricin to limit catabolic cytokine expression, restore synovial fluid lubrication and reduce clinical signs of lameness in equine IL-1ß-induced synovitis.