Pneumonia, laminitis studies get research backing

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Research into pneumonia and laminitis are among horse research projects approved for funding by the Grayson-Jockey Club Research Foundation for 2012.

The foundation’s board of directors approved backing for 16 research projects for the year, which will receive a total of $US845,646.

The funding will cover the second year of eight projects started in 2011, and the board selected eight new projects to be launched in 2012.

The new research projects cover a wide range of problems that can affect horses of any breed or discipline.

They include foal pneumonia, laminitis, vitamin D’s role in immunity, and stem cell therapy.

Universities receiving funding for new projects are the University of Georgia, Ohio State University, Michigan State University, the University of Florida, Cornell University, the University of Kentucky, and the University of Pennsylvania.

The foundation is traditionally the nation’s leading source of private funding for equine medical research, and the new projects brings the foundation’s total since 1983 to 287 projects funded for $19 million across 40 universities.

One of the researchers is the recipient of the Elastikon Equine Research Award. It is funded in part through a contribution by Johnson & Johnson’s Consumer Products Company, which makes Elastikon tape and other equine products.

Selected to receive the award for 2012 is James Belknap’s project, “Laminar Signaling in Supporting-Limb Laminitis”.

Supporting-limb laminitis refers to the phenomenon that a horse with an injured leg runs the risk of developing laminitis in the opposing leg because of the extra weight bearing the non-injured leg endures.

Belknap’s work will seek additional understanding of what medications or treatments might prevent this phenomenon.

Another special award presented by the Grayson-Jockey Club Research Foundation is the Storm Cat Career Development Award. The annual award of $US15,000 goes annually to a promising young individual potentially headed on a career path of equine research.

The award is named in honour of the stallion Storm Cat and is personally underwritten by foundation board member Lucy Young Hamilton, whose family stood Storm Cat at Overbrook Farm.

The 2012 Storm Cat award winner is Dr Alice Stack, who is researching exercise-induced pulmonary hemorrhage with Dr Fred Derken at Michigan State University. The Storm Cat award is in addition to the eight other projects being launched.

 

Determinants of Immune Protection Against Babesia equi (Piroplasmosis)

Dr. Robert H. Mealey, Washington State University -Second Year

Babesia equi is a blood parasite in horses that causes piroplasmosis. The parasite is spread by ticks. Many believed piroplasmosis to be foreign to the United States, while others anticipated it was only a matter of time until it appeared in this country. Recent outbreaks in several states proved the second opinion correct and emphasize the critical need for additional means of disease prevention and control. Persistence of the disease will cause abortions and mortality. In addition to these humane considerations, the imposition of export restrictions and interstate movement restrictions would have an enormous economic impact on the entire horse industry. No vaccine currently exists, and the type of immune response such a vaccine would have to elicit has not been established. The overall goal of this proposal is to identify the immune responses necessary to protect horses against infection. The researchers will perform a comprehensive analysis of immune responses following infection, treat horses with drugs to clear the infection, and determine if the treated horses are resistant to re-infection. They will identify the types of immune responses that are important in protection. The studies will determine if treated horses develop immunity, which alone is important information and will also greatly facilitate the identification of protective vaccine targets.

AAV-IRAP Gene Therapy to Prevent Osteoarthritis

Dr. Laurie Goodrich, Colorado State University -Second Year

Osteoarthritis is a common affliction in horses, and current methods of treatment are effective only in reducing the pain, at best. This proposal will utilize gene therapy, which is a technique in which cells can be genetically modified or “re-programmed” to produce beneficial protein that will allow cartilage to heal. The initials in the project title stand for Adenoassociated Virus and Interluken Receptor Antagonist Protein. If cells in the joint could be re-programmed to produce IRAP, the devastating effects of joint inflammation could be halted and the progress of osteoarthritis could be reversed. These researchers’ preliminary work utilizing AAV-IRAP suggests that cells of joints are easily re-programmed to produce beneficial protein. The aims of this project is to define the most appropriate dose of AAV-IRAP that will result in effective levels and answer the question of whether this approach can prevent osteoarthritis in the horse.

Digital Hypothermia in Laminitis: Timing and Signaling

Dr. James Belknap, The Ohio State University -Second Year

The most recent figures from a study involving the USDA and State Veterinary Medical Officers project that at any given time laminitis affects 8 of every 1,000 horses in the United States. Based on the American Horse Council survey that there are 9.5 million horses in the nation, that would indicate 76,000 horses being affected at any given time. Of those affected, the USDA survey found that 4.7% died or were euthanized, or about 3,572 deaths from laminitis annually. The authors of this project report that “an integrated research effort over the last decade has enhanced the current understanding of the pathophysiology of equine sepsis-related laminitis (one of numerous causes of the disease). This has mirrored progression of sepsis research in human medicine by moving from (an earlier) concept . . .to determining that a marked inflammatory injury takes place and is likely to play a prominent role in tissue injury and subsequent failure.” However, there have been persistent failure of systemic therapies for organ/laminar injury in both human and equine medicine. One advantage laminitis presents is that it effects the hoof rather than visceral organs, lending itself to artificial cooling more readily. In a present project funded by the Foundation, digital hypothermia (cooling of the hoof) prior to onset of carbohydrate overload-induced equine sepsis resulted in dramatic decrease in laminar inflammatory signaling. The next goal is to find pharmaceutical therapies which can accomplish the same without the cumbersome aspects of maintaining constant hypothermia to the equine hoof (hooves).

Laminar Energy Failure in Supporting-Limb Laminitis

Dr. Andrew Van Eps, University of Queensland -Second Year

A frequent and disheartening result of injury repair is that the leg opposite the one injured develops laminitis. This is known as supporting-limb laminitis and is what eventually caused Barbaro to be euthanized. Although it is a common occurrence, the mechanisms of the malady have not been established. This project is headed by a young researcher, but the co-investigators are world renowned Drs. Dean Richardson and Chris Pollitt. The project involves testing the hypothesis that supporting-limb laminitis is a result of reduced blood supply to the connection between hoof and bone (lamellar tissue). Further, that the blood supply in normal circumstances is encouraged by a regular loading and unloading of the legs and hooves (alternating which one is bearing the most weight). Injury to one leg interrupts that alternating pattern. The researchers will test the hypothesis with a state of the art, minimally invasive technique known as tissue mycrodialysis in conjunction with three dimensional computed tomography to develop effective methods of preventing or minimizing lamellar tissue energy failure. Comments in the Research Advisory Committee evaluations included “may well provide immediately applicable strategies to prevent supporting-limb laminitis” and “really nice grant, new idea about a devastating problem.”

Investigation of Cell and Growth-Factor Dependent Tenogenesis

Dr. Martin A. Vidal, University of California-Davis -Second Year

The crux of this study is to test preliminary indications that a newly developed in vitro tendon/ligament culture model will prove effective at determining the optimal cell type from bone marrow, fat tissue, umbilical cord, tendons, ligaments, and muscle to use in tendon and ligament repair. The model also will allow investigators to learn the early molecular and cellular signals in tendon and ligament tissue formation. The author states that current methods of healing result in inferior scar tissue and reinjury rates ranging from 23% to 67%. Transforming growth factor (TGF) combined with platelet rich plasma will be utilized, and tests will be done on how they affect tissue growth, strength, and composition. ”

Stem Generation of Equine Induced Pluripotent Cells for Regenerative Therapy

Dr. Lisa Fortier, Cornell University- Second Year

Stem cell based therapies are among avenues being tested with the goal of tendon cell regeneration to address tendonitis. The types of stem cells used so far may improve the structure of tendon healing, but appear to have limited regenerative ability or are limited due to potential issues of immune rejection. The author explains that, “ . . . this proposal is to generate induced pluripotent stem cells (iPS cells) from equine adult dermal fibroblasts. iPS cells are the only stem cells that are both pluripotenent and autogenous, making them the most useful for clinical application. The expectation is that the results of the studies in this proposal will provide the first published description of the generation and characterization of equine iPS cells.” This is part of a process of testing the overall hypothesis that equine iPS cells will enhance tendon regeneration in cases of tendonitis. Also, “the technical expertise gained in this study could be used in the future to generate autogenous iPS cells for use in equine cartilage and neuronal regeneration studies.”

Early Diagnosis of Recurrent Laryngeal Neuropathy

Dr. Jonathan Cheetham, Cornell University -Second Year

Laryngeal neuropathy, or “roaring,” is estimated by the author to affect 8% of race horses and a higher percentage of sport horses. This researcher over the last three years has developed two non-invasive procedures to assess the cricoarytenoid dorsalis (CAD) muscle and the nerve that supplies it. The CAD muscle is the only muscle that opens the larynx during exercise. The present proposal will validate two diagnostic tests for early detecting of roaring in horses. The ability to identify young horses which are predisposed to become roarers would enable surgical intervention to restore the nerve supply before atrophy and fibrosis of the CAD muscle occurs.

Hemorrhagic Anovulatory Follicle Syndrome

Dr. Eduaro Gastal, Southern Illinois University -Second Year

Hemorrhagic anovulatory follicles (which prevent ovulation from occurring) are an ongoing problem and, this researcher suggests, have become more commonplace in recent decades. He conjectures that use of drugs to shorten the estrous cycle and induce ovulation might have aggravated the problem among intensely management broodmares. This study will induce HAFs and create the opportunity to study the “systemic, intrafollicular, and cellular changes regarding hormones, growth factors, receptors, and enzymes when compared to follicles that ovulate normally.” In other words, the researchers seeks to “uncover the mysteries behind the HAF syndrome.”

Liposomal Gentamicin for the Treatment of R. Equi

Dr. Steve Giguere, University of Georgia – First Year (2 Year Grant)

Pneumonia is the leading cause of death in foals in the United States, and Grayson-Jockey Club Research Foundation has been funding numerous projects on it in recent years. This project scored highest of the record 73 projects submitted. There is no vaccine yet for foal pneumonia caused by Rhodococcus equi and, even with the recommended treatment of macrolide and rifampin, farms tend to see a 30% death rate from cases. Moreover, Rhodococcus equi, the bacterium which is the leading cause of foal pneumonia, is showing resistance to the treatments. Gentamicin has been demonstrated in laboratories to be effective against R. equi, but because it is a water-soluble drug it is not effective in the actual patient. This project is based on the hypothesis that addition of liposomes to gentamicin will make the treatment more successful. The various stages of the project will include tests to determine not only the effectiveness of liposomal gentamicin but also any effects of repeating dosing. The impact of this study could be lead to a practical regime for using a powerful new drug for treating R.equi pneumonia.

Pulmonary Microvascular Function and EIPH

Dr. Fred Derksen, Michigan State University– First Year (2 Year Grant)

Dr. Derksen has received previous Grayson grants and continues the quest to determine the causes of Exercise Induced Pulmonary Hemorrhage (EIPH). This project will address the recent discovery that tiny blood vessels in the lungs of EIPH-affected horses are scarred, and it is believed these scarred blood vessels play a role in causing EIPH, being the sourse of the hemorrhage. The main purpose of the project is to investigate how these tiny blood vessels function and, importantly, whether they are the site of action of furosemide (Lasix). This knowledge will be critical to understanding whether an effective prevention or treatment of EIPH can be produced.

Vitamin D and Innate Immunity in the Horse

Dr. Mary Hondalus, University of Georgia– (1 Year Grant)

Foals have lower vitamin D levels than mature horses, and sick foals may have lower levels yet. This project will seek to verify the likelihood that this leaves them more susceptible to various diseases, as vitamin D has recently been revealed to be critical for protection from diseases like R.equi that infect macrophages. The hypothesis is that the immune system of horses are vitamin D responsive, i. e., that a pathway to the killing of harmful bacteria is connected to vitamin D. The author states that “The identification of a pathway whose stimulation enhances the innate bacteria killing capacity within the immune system would be ground breaking.” This one year project will test this first hypothesis, and success would lead to a series of new treatments for enhanced intervention in disease.

Laminar Signaling in Supporting-Limb Laminitis

Dr. James Belknap, The Ohio State University– First Year (2 Year Grant)

A recent USDA study indicates that approximately 1% of all horses in the USA suffer from laminitis at any given time, and approximately 5% of those animals die or are euthanized while many others remain crippled. Of the conditions which create laminitis, the development of the disease in the supporting limb of an already injured horse is one of the worst, since it is believed that 50% of those cases result in euthanasia. The author reports that while there are hundreds of published papers in the literature about other forms of laminitis, reports on supporting-limb laminitis are restricted to clinical reports and case studies. This project will “introduce a novel, non-painful model of supporting-limb laminitis and will allow for cutting edge bench research techniques to not only (1) test the current hypotheses on the cause of laminar failure, but also (2) provide an unbiased technique to determine the cellular events that occur . . .” The investigator has performed a number of laminitis project for Grayson and the USDA, and has a well developed set of tools and techniques including laser microdissection of frozen laminar cells and an advanced “functional genomic” technique called RNA-Seq. By applying these techniques that have previously characterized laminitis caused by sepsis or metabolic syndrome to support limb laminitis, we will get our first understanding of what kind of drugs and treaments might prevent it. This grant was selected by the board to receive the sixth annual Elastikon™ Equine Research Award.

Pharmacokinetics of Ceftiofur Sodim in Equine Pregnancy

Dr. Margo Macpherson, University of Florida – (1 Year Grant)

Foals which are born prior to the last week of normal gestation have high death rates, and the most important cause of abortion and premature delivery is bacterial placentitis (infection of the placenta). Various treatments can increase the success rates of such cases, including antibiotic treatment but this researcher’s experience is that 50% of those mares still have bacteria in the uterus. This project will test the hypothesis that a different antibiotic, ceftiofur sodium, will be an improvement and will achieve effective levels in the uterine tissues during pregnancy. This antibiotic has been shown to be highly effective in killing various kinds of bacteria, particularly those that cause placentitis. “With positive results from this study,” states Dr. Macpherson, “we will have confidence using this drug in pregnant mares. Further, these results will move the equine community one step closer toward reducing foal losses due to placental infections.”

Stem Cell Homing after IV Regional Limb Perfusion

Dr. Alan Nixon, Cornell University– First Year (2 Year Grant)

“The initial fervor associated with stem cell therapies has been tempered by mediocre clinical results,” states Dr. Nixon, long recognized as a key leader in quest to maximize use of stem cells. “More can be done, including pre-differentiation, gene-directed lineage targeting, and more efficient delivery.” This proposal will deliver by “local vein injection, to back-flow to bowed tendon and other disease conditions such as founder and traumatic arthritis.” Transplanted cells then exert normalizing and restorative effects . . .” The long-range goal is to provide a simplified approach to stem cell therapy. We cannot do this without verification of cell homing and impact. (The project) will map stem cell distribution in the tendons, ligaments, and joints of the forelimb after direct venous injection.”

Do Non-Steroidal Anti-Inflammatory Drugs affect the Immune Response to Vaccination in Horses?

Dr. David Horohov, University of Kentucky– (1 Year Grant)

Non-Steroidal Anti-Inflammatory Drugs (NSAIDS) are sometimes prescribed prior to a vaccination in order to reduce the chance of an adverse reaction to that vaccination. Dr. Horohov observes that the reasoning behind this “might seem sound,” but there is the concern that the NSAIDs might have the unintended consequence of actually impeding the ability of the horse’s system to respond to the vaccination as intended. This project will determine the effect of NSAIDs on the ability of a horse to benefit from a commercial influenza vaccine. The results will help veterinarians and horse owners to make more informed decisions regarding use of the NSAIDs when vaccinating.

Towards a Treatment for Testicular Degeneration

Dr. Regina Turner, University of Pennsylvania– First Year (2 Year Grant)

In previous work funded by the Foundation, Dr. Turner determined that idiopathic testicular degeneration (ITD)—referring to the adverse effects of ageing of the testis—is a defect residing within the testis itself, rather than reflecting an external problem. That project also found that contact with young, healthy testicular tissue significantly improves the condition of the ITD-affected cells when they are cultivated together. This is a technique known as “xenografting.” The next step, to be addressed in this project, is to determine if integration of young-cell populations will improve function and sperm production in the old cells. A second aim of the project is to employ “the most modern techniques” to identify all the genes whose foundations are altered in the old degenerate tissue compared to healthy tissue.

Storm Cat Career Development Award

“Pulmonary Microvascular Function and EIPH,” Dr. Alice Stack, Michigan State University. One year, $15,000

The Sixth Annual Storm Cat Career Development Award recipient is Alice Stack, a post-doctoral fellow from Michigan State University. Dr. Stack will be working with Dr. Frederik Derksen.

The $15,000 Storm Cat Career Development Award is underwritten by a board member, Mrs. Lucy Young Hamilton, and is named in honor of the distinguished stallion Storm Cat, which was bred by Mrs. Hamilton’s father, W. T. Young, and stood at the family’s Overbrook Farm in Kentucky. The Storm Cat Career Development Award was created to provide an early boost to an individual considering a career in equine research.

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