For the first time in its history, the Grayson-Jockey Club Research Foundation will distribute in excess of $1,000,000 for research grants in 2007.
The foundation's board of directors recently approved 13 new projects, including three devoted to the study of laminitis, and renewed funding for eight others that are already underway. The total allocation for research is $1,105,045.
The board also issued a special call for herpesvirus research proposals.
"We have had as a goal the ability to fund a million dollars of research in a single year," said Edward L. Bowen, president of the foundation. "With the help of generous donors, we have not only reached, but exceeded that level for 2007."
The 2007 funding brings the foundation's total since 1983 to more than $14 million, which has underwritten 223 projects at 34 universities.
The laminitis-related projects are:
• Early treatment of laminitis with lidocaine, conducted by collaborating researchers at The Ohio State University and University of Massachusetts under the direction of Dr. J.K. Belknap;
• Factors that trigger the onset of laminitis, conducted by a team at the University of Georgia headed by Dr. T.P. Robertson; and
• Levothyroxine as a treatment for insulin resistance, conducted by Dr. Nicholas Frank of the University of Tennessee in association with Dr. Ray Boston of the University of Pennsylvania. Insulin resistance increases susceptibility to pasture laminitis.
In addition to laminitis, subjects addressed by the new slate of projects include an improved method of preventing infection in fracture repair, a study to be undertaken by Dr. Dean Richardson at the University of Pennsylvania's New Bolton Center.
A project at Colorado State University has been designated as recipient of the ElastikonTM Equine Research Award provided by Johnson & Johnson Consumer Products Company. Johnson & Johnson made a grant to the foundation in the name of its elastic tape product ElastikonTM, and this grant will be applied to the funding of Dr. Chris Kawcak's project on the shape of the fetlock joint. The ability to detect and evaluate minute changes in shape will help managers and trainers of horses differentiate between normal progression and the shape and type of change associated with oncoming condylar fracture. Dr. Kawcak will work with colleagues at the Animal Health Trust and University of Liverpool in England.
The call for additional herpesvirus research is a continuation of the foundation's longtime funding of research on that disease, which accounted for numerous equine deaths and quarantines at several locations during 2006. Herpesvirus-related allotments of $50,000 for 2007 and again in 2008 have been authorized by the foundation's board of directors, chaired by Dell Hancock.
A complete list of the 2007 research projects, which is also available at http://www.grayson-jockeyclub.org/grantsDisplay.asp?section=4, follows:
Reducing wound infections of orthopedic surgeries
Investigators: Dean Richardson, Thomas Schaer, Noreen Hickok, Christopher Adams
University of Pennsylvania and Thomas Jefferson University
Dr. Dean Richardson has become well known as a surgeon and attending veterinarian in the Barbaro case. He is also an accomplished researcher who has been funded by Grayson-Jockey Club Research Foundation in the past and who served a term on the foundation's Research Advisory Committee. Dr. Richardson will serve as principal investigator, overseeing colleagues in this study. He notes that "implant related infections result in repair breakdown and often loss of many long-bone fracture patients." This project utilizes the concept of "smart implants" being pursued in human medicine. Wound infection of orthopedic surgical procedures involving metal prostheses is a major cause of fixation failure in equine fracture repair. Recent developments such as limb perfusions with antimicrobials, use of minimally invasive techniques, and antimicrobial impregnation of metal prostheses have helped in prevention and treatment of infections. These investigators seek to improve the record further with an antibiotic known as vancomycin, which they propose can be bonded to stainless steel (prostheses). They will then demonstrate that bone healing will not be compromised by this treatment of the prosthesis.
Control of Rhodococcus equi pneumonia using gallium
Investigators: Keith Chaffin, Noah Cohen, Ronald Martens
Texas A&M University
Foal pneumonia remains a major cause of illness and death in foals. Prevailing impression is that 9% of foals are affected and that 12% of those do not survive. This team has shown the potential benefit of gallium against this disease in an earlier Grayson-Jockey Club Research Foundation grant. They now propose a trial to test the following: Gallium is well absorbed in neonatal foals following oral administration, and a dose of 20 mg/kg will result in serum concentrations of gallium that will suppress the growth of or kill intracellular R. equi organisms. They also hope to show that daily doses of the gallium for the first 14 days of life will reduce the prevalence of the disease.
Blood supply to the mare's uterus is related to infertility: Evaluation and Treatment
Investigators: Irwin Liu, Eugene Steffey
University of California-Davis
It has long been suspected that infertility in older mares is due to degeneration of the uterine lining (endometrium). These investigators have shown evidence that the problem is related to damage to the uterine blood vessels, namely loss of elasticity and reduced blood perfusion of the uterus. They have developed methods of measuring blood flow and means of improving that flow with anticoagulants such as aspirin. This project is designed to verify the differences in blood flow and in blood vessel function between older, infertile mares and their younger counterparts. A comparison of blood flow between the groups is accomplished with fluorescent microspheres injected into the circulation. This is a well thought-out step in determining causes of infertility and reversing the problem.
Levothyroxine as a treatment for insulin resistance in horses (toward a defense against laminitis)
Investigators: Nicholas Frank, Ray Boston
University of Tennessee and University of Pennsylvania
Approximately one-half of horses who develop laminitis are on pasture when the disease develops. Sugar content of grass is believed to trigger pasture laminitis, while insulin resistance accounts for some horses being more susceptible than others. This team has already shown that levothyroxine (LT4) can be safely administered to horses, induces weight loss, and increases insulin sensitivity. It is even more effective when given to horses with insulin resistance (IR), obesity and laminitis. This disorder is referred to as equine metabolic syndrome (EMS), and the study of the disorder reveals valuable insights into the relationship between insulin sensitivity, factors such as body fat mass, thyroid hormone status and laminitis.
This study seeks to expand the numbers of horses from the eight that have been reported up to 20, to gain statistical significance. Then, statistically sound results will be available for further studies on LT4 and its effects on laminitis sensitivity. This will be a pivotal study because the results will establish LT4 as the first effective treatment for IR in horses that are highly susceptible to laminitis. This would confirm the authors' hypothesis that LT4 can be used to prevent laminitis in at-risk horses by improving insulin sensitivity.
Promoting specific immunity in foals
Investigators: D.W. Horohov, C. Merant, C. Breathnach
University of Kentucky
Very young foals are susceptible to numerous bacterial and viral diseases, in spite of high levels of antibody from colostrum. Rhodococcus equi is a prime example. Foals exhibit an age-dependent susceptibility to this infection, which is probably associated with immaturity of the foal's immune system. These investigators have characterized this defect as a deficit of a specific cytokine produced by T cells, which protect against R. equi. In this project, they plan to study accessory cells in foals over time and compare these data with similar cells in older horses. They will be searching for differences in the immune response of these cells, determining methods of enhancing immunity by the cells and their protein production, and measuring the response of the foal's cells to these treatments. The overall goals will include treatment of the foals with immune modulators to strengthen their immune capability.
Normal and abnormal functions of specific proteins in stallion semen
Investigators: M.H.T. Troedsson, W.C. Buhi, J.P. Verstegen, M.L. MacPherson
University of Florida
These researchers observe that "the recent finding that a specific protein in seminal plasma protects viable sperm cells from being destroyed by uterine inflammatory cells is a landmark discovery that warrants further investigation." Identification of seminal plasma proteins that regulate the interaction between spermatozoa and the mare's reproductive tract enables understanding of basic semen biology and of biochemical causes of infertility and sub-fertility in stallions. The investigators propose to establish normal values for these proteins in fertile stallions and then test sub-fertile stallions for deficiencies of the proteins. The long-term goal is to characterize the biological function of seminal plasma components that are important to fertility.
Calcium/magnesium and hormones in septic foals
Investigators: R.E. Toribio, C. Kohn, S. Hurcombe, Nathan Slovis
The Ohio State University and Hagyard-Davidson-McGee, Lexington, KY
Sepsis, or overwhelming total body inflammation, is the number one cause of foal mortality. Low calcium and low magnesium are frequent findings in septic foals. Reduced calcium levels are associated with seizures, intestinal inactivity, respiratory failure, cardiac failure and death. Little information on the prevalence of hypocalcemia or hypomagnesemia has been documented. Thus, the investigators plan to measure the calcium and magnesium levels in septic and normal foals, and to measure blood concentrations of the hormones that regulate these elements, followed by comparisons in survival rates. One hundred septic foals will be evaluated, as well as 20 healthy foals and 30 sick foals, but not septic foals. These cases are available at The Ohio State Veterinary Hospital and at the Hagyard hospital in Lexington. The information gleaned will advance understanding of foal sepsis, and hopefully guide future interventional studies.
Safe management of pain in adult horses with Tramadol
Investigators: A.J. Stewart, D.M. Boothe
Auburn University
Pain control in the adult horse has been managed with non-steroidal drugs such as Phenylbutazone or Flunixin, both of which have serious side effects in kidney and gastrointestinal damage. Morphine causes arrested gut motility. Opioid patches and continuous rate administration of lidocaine or butorphanol is very expensive.
Tramadol is a centrally acting analgesic that has been used clinically for pain control in humans and dogs for 20 years. It has no effect on the GI, cardiovascular or respiratory systems, and is not a controlled substance.
This study will evaluate oral Tramadol, from a pharmacological perspective, monitor serum levels, and define any side effects. Internal medicine specialists are very anxious to have a drug of this caliber available for the horse.
The shape of the fetlock joint is important to incidence of joint disease and injury
Investigators: Chris Kawcak, C. Puttlitz, C.W. McIlwraith, K. Parkin, K. Morgan
Colorado State University, Animal Health Trust, Newmarket, England, & University of Liverpool
These investigators hypothesize that horses suffering condylar fracture have abnormal geometric properties of the joint, compared to horses without fracture. Condylar fracture is a very common cause of breakdown, and thus can be studied in large numbers. The investigators have access to many post mortem specimens of fetlock fracture.
To accomplish the correlation of the fracture to its geometric properties, the investigators will make a series of detailed measurements of the condylar surface, and compare them to the surface of the non-fractured fetlock. From these data, they will develop a computer model of the shape of the fetlock and the change of shape in response to loading.
Thus the variations in joint shape can be documented in the process of preparing the horse for racing. These components will allow a determination of the threshold of geometric properties that can lead to condylar fracture. Then, progressive changes from training or racing can be evaluated in comparison to the computer model, thus providing useful early warning of potential for serious injury.
Genetic basis for establishment of pregnancy in mares
Investigators: A. Ealy, M.H.T. Troedsson
University of Florida
This project is directed at the specific changes that occur in the developing embryo of the horse and the uterus of the mare that signal the occurrence of pregnancy. The practical application is that understanding the specific events of maternal recognition of pregnancy will enable better defense against early embryonic loss. The investigators have developed a gene-based array of the proteins involved in the key event of pregnancy recognition.
Early treatment of acute laminitis with lidocaine
Investigators: J.K. Belknap, S.J. Black
The Ohio State University and University of Massachusetts
The investigators have found similarities between acute laminitis and septic inflammation in the horse. There is some real potential benefit in treating early cases of laminitis with intravenous lidocaine (a local anesthetic). They feel the drug will decrease the changes leading to laminar failure. The evaluation will include a comparison to placebo treatment. Cellular features of acute laminitis and other characteristic changes of tissues involved will be studied. If lidocaine is found to be effective in blocking some of the mechanisms of early laminitis, it will be a valuable addition to the few tools available in dealing with this prevalent malady.
Factors that trigger the onset of acute laminitis
Investigators: T. P. Robertson, J.N. Moore, D.J. Hurley, J.F. Peroni, T.F. Krunkosky
University of Georgia
This group of researchers is pushing on toward an understanding of basic factors leading to acute laminitis. The basis for this study is the observation that the processes leading to acute laminitis are initiated when specific white blood cells leave the circulation and enter the soft tissues in the laminae of the hoof and trigger the inflammatory processes, including damage to blood vessels. This grant will provide the tests that confirm the theory and eliminate certain reactions other than laminitis that could be caused by the challenges. This would be a major step in solving the puzzle of the origins of laminitis
Reduce pin loosening in horses with cannon bone fracture
Investigators: T.B. Lescun, D.C. Van Sickle, G.E. Moore, D. Baird
Purdue University
The project attempts to evaluate a coating (Hydroxyapatite) for transfixation pins used to treat 3rd metacarpal fractures. The coating is alleged to improve the bond between the pin and bone by promoting a reaction known as osteointegration. This will be confirmed by monitoring the fractures for healing by radiology, torque measurement and clinical observation. Measuring the forces needed to extract the pins after eight weeks post-surgery will be monitored by pin extraction torque. The stability of the coated pins will also be evaluated and compared with that of non-coated pins. This appears to be a very well-thought-out project with clear goals for improving fracture healing using this coating.
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