The Grayson-Jockey Club Research Foundation will devote almost $1.5 million for nearly two dozen projects in 2023, its board of directors announced.

The foundation will spend $1,498,077 on 12 new projects, nine continuing projects at 13 universities, and two career development awards. Eight of the 21 research projects are foot and leg related. The foundation has spent more than $34.1 million on 426 research projects at 45 universities since 1983. The research projects related to the foot and leg are detailed below.

Transcriptomic Response to Osteoarthritis

Colorado State University researcher Lynn Pezzanite receives a 2-year grant to “highlight the role that cells of the immune system play to contributing to disease progression of osteoarthritis [OA] toward the goal of developing treatments for each stage of disease.”

Although osteoarthritis is estimated to affect as much as 80% of horses that are 15 years and older, treatment options are limited and its progression is not fully understood.

“The purpose of this study is to determine how the genetic code of cells, particularly cells of the innate immune system, changes during early osteoarthritis progression and how those values correlate to levels of inflammatory biomarkers, called cytokines, in joint fluid,” according to Pezzanite. “This work will integrate new technologies including single-cell RNA sequencing and multiplex biomarker analysis towards this goal. This study will highlight the role of immune infiltration contributing to disease biology in OA progression towards the overall objective of developing treatments tailored to disease stage.”

Efficacy of Recombinant Equine Lubricin for Osteoarthritis

Heidi Reesink, a Cornell University researcher, will receive a 2-year grant to “assess efficacy of recombinant equine lubricin (rEqLub) in mitigating equine joint disease and identify gene and protein pathways affected by rEqLub in equine joints.”

Research finds that OA develops in as many as 50% of fractures involving the joint in human patients, as well as similar equine fractures. Several tissues within the joint are involved in OA, including articular cartilage, synovial membrane, and the surrounding joint capsule and ligament tissues.

“The long-term objective of this proposal is to translate lubricin therapy to equine clinical patients,” according to Reesink. “We hypothesize that equine specific recombinant lubricin (rEqLub) can improve joint inflammation and arthritis by means of its anti-inflammatory and lubricating properties. In Aim 1, the efficacy of equine-specific synthetic lubricin to ameliorate the development of osteoarthritis in a surgical disease model. In Aim 2, we will study the signaling pathways that are affected by rEqLub in healthy equine fetlock joints, which will help identify mechanisms by which lubricin can protect joint health. We expect these studies to provide a baseline for the establishment of efficacy of lubricin joint therapy in the horse, which will springboard evaluation of lubricin therapy to future clinical trials in equine patients.”

Treatment of Meniscal Injury with Mesenchymal Stem Cells

Cornell University researcher Aimee Colbath receives a 2-year grant to “determine whether intra-articular mesenchymal stem cells lead to improved meniscal healing, providing an immediate impact on how veterinarians treat equine meniscal disease.”

Meniscus injuries result in a relatively poor prognosis for equine athletes to return to their previous level of performance. Recent studies are mixed on whether horses benefit from mesenchymal stem cells. This study aims to fill the gaps.

“We will conduct a randomized, controlled, blinded prospective study evaluating the use of intra-articular mesenchymal stem cells for treatment of meniscal injury using a novel, experimental model of meniscal disease,” according to Colbath. “This study will achieve two important objectives. Firstly, it will establish this experimental model of meniscal disease which can be used now and in the future for evaluating the effectiveness of intraarticular treatments for meniscal disease. Secondly, the study will evaluate the effectiveness of intra-articular MSCs for meniscal disease using multiple outcome measures including lameness, joint fluid characteristics, diagnostic imaging outcomes, joint evaluation following euthanasia and cellular tissue (histologic) outcomes. The study will have an immediate impact on the treatment of meniscal disease in the horse by determining the efficacy of intra-articular MSC use, and a longer-lasting impact by providing an experimental model for future investigation of therapeutic interventions.”

Stem Cell Neotissue Implants for Equine Tendon Healing

Mandi J. Lopez, a researcher at Louisana State University, receives a 2-year grant to “determine if viable neotissue implants generated from stem cells will augment current therapies to treat debilitating tendon injuries in equine athletes and companions.”

Lost training days and early retirement among equine athletes are the most common results of tendon and ligament injuries. Local cells rarely assist with healing in adult horses, which helps lead to slow and incomplete healing. Recent research finds that stem cells directly implanted into tendon tissue go to the injury and produce healthy tissue rather than scar tissue.

“There are limited ways to apply stem cells to tendon and ligament injuries or to keep them at the injury site during the healing process,” according to Lopez. “We propose to overcome some of the hurdles to cell therapies for tendon injuries by turning stem cells into tendon cells that produce normal tendon tissue around them. Specifically, we developed a unique system that stimulates stem cells to become tendon cells and produce tissue after 21 days in highly customized fluid flowing through chambers that contain the cells on collagen templates. The proposed studies will confirm generation of tendon cells in new tissue that can be stored and shipped frozen so that it can be used promptly whenever and wherever necessary. The ability of the tissue to promote tendon healing will also be confirmed in equine tendon injuries. The ultimate goal of this work is to create a reproducible mechanism to generate tendon tissue implants that can be clinically applied to facilitate healing and restore normal limb function in equine athletes and companions.”

PET MRI Sport Horse Fetlock

Mathieu Spriet, a University of California, Davis researcher, receives a 1-year grant to “compare 18F-NaF Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) for assessment of fetlock injuries in sport horses.”

Although ultrasound and X-rays are most commonly used in the assessment of fetlock injuries, early bone lesions might not be recognized. Preventing the progression of joint disease relies on early identification of the lesions. The study will compare PET and MRI in to provide the early identification.

“This proposal suggests performing both 18F-NaF PET and MRI of both fetlocks in a sport horse population with lameness localized to the fetlock,” according to Spriet. “The aims of the study would be to describe the 18F-NaF PET findings in a sport horse population and compare with MRI. A total of 35 regions of interest including specific articular bone sites and areas of attachment of ligaments will be assessed independently both on PET and MRI by five independent experienced observers. Correlation between PET findings and both low-field and high-field MRI will be assessed. An additional aim of the study would be to assess an Artificial Intelligence (AI) software specifically designed to assess equine fetlock PET. This program will provide automated measurements of bone turn-over. These measurements will be correlated with the subjective grades from the observers. Based on the knowledge from racehorse studies and early clinical use of 18F-NaF PET in sport horses, we expect to demonstrate a good agreement between 18F-NaF PET findings and MRI abnormalities. It is also likely that 18F-NaF PET would identify early changes in articular bone and at the attachment of ligaments prior to the identification of MRI changes. The AI data would likely confirm and refine the assessment from the expert observers and ultimately contribute to simplify and speed up the assessment of PET scans.”

Immunomodulation and Exosomes to Enhance Tendon Healing

Sushmitha Durgam, an Ohio State University researcher, receives the funding for the second year of research that “aims to characterize M1 and M2 macrophage-derived inflammatory factors and assess their impact on superficial digital flexor tendon tenocyte activities while examining the potential of extracellular vesicles/exosomes to enhance tendon healing.”

Inflammation and poor intrinsic tendon healing capacity results in poor quality of tendon repair, which results in decreased elastic strength and an increase in reinjury.

“Growing evidence suggests that immunomodulation is an effective strategy to improve the quality of tendon repair,” according to Durgam. “Macrophages are key immune cells that modulate inflammation, pain during healing and therefore, this research will characterize macrophage-derived inflammation, and identify biological/cellular mechanisms affecting tenocyte activity and, subsequently contribute to tendon degeneration during healing. This research is will also help evaluate the beneficial effects of a novel off-the-shelf biologics/ regenerative therapy for tendon healing as several recent studies have demonstrated that immunomodulation is key mechanism to enhance tendon healing. Collectively, this work will impact develop therapies that can improve tendon injury outcomes in horses.”

Motion of the Proximal Seasmoid Bones on Uneven Footing

University of California, Davis researcher Susan Stover receives second-year funding for a study that “proposes to determine how hoof conformation, shoeing, and uneven racetrack surfaces could contribute to fetlock breakdowns.”

“Shoeing, uneven footing, and other factors (e.g., turning a corner) affect the three-dimensional motions of P1 relative to the cannon bone,” according to Stover, a member of the International Equine Veterinarian Hall of Fame. “We do not know if these factors affect proximal sesamoid bone motion. Uneven footing has been caused during laboratory tests by wedges placed under the inside or outside of the hoof, but banked racetracks, unbalanced hooves, and/ or unharrowed racetracks likely have a similar effect. Since non-sagittal plane motions of P1 relative to the cannon bone are exaggerated by uneven footing, we believe that proximal sesamoid bone motions will also be exaggerated by uneven footing due to the soft tissue connections to P1 and the joint articulation with the cannon bone. Therefore, the primary goal of this proposal is to determine how uneven footing affects the motion of the proximal sesamoid bones relative to the cannon bone. The secondary goal is to determine if the ligaments connecting the PSBs to P1 are the mechanism for the motions. These research goals will improve our understanding of how proximal sesamoid bone fracture may be linked to hoof conformation, shoeing, and racetrack surface conditions.”

Sirolimus for the Control of Insulin Dysregulation

University of Pennsylvania researcher Andrew van Eps receives second-year funding to “evaluate the drug sirolimus (a potent suppressor of insulin production) for the treatment of insulin dysregulation (the most important cause of laminitis) in horses.”

“We hypothesize that treatment with sirolimus will prevent high blood glucose in response to ingested carbohydrate in horses with both experimentally-induced and naturally-occurring ID and will be safe and well tolerated,” according to van Eps, a member of the International Equine Veterinarian Hall of Fall. “Using an established experimental model of ID, we will test the effects of 2 different dose rates of oral sirolimus on insulin dynamics in response to oral sugar challenge. We will then test the effects of oral sirolimus treatment in horses with naturally occurring ID using a randomized, placebo-controlled crossover study. Blood sirolimus concentrations as well as hematological parameters and serial clinical evaluations will be used to monitor for any adverse effects. We anticipate that this study will provide fundamental information on the efficacy and safety of sirolimus for the treatment of ID in horses. In line with our preliminary data, we expect that sirolimus therapy will rapidly and profoundly suppress insulin production in response to ingested sugar, without causing adverse effects. The results of this study have the potential to drive the development of novel treatments for insulin control and prevention of laminitis in the horse.”