Current Research
Grayson-Jockey Club Research Foundation will fund 17 projects
in 2013, totaling $874,024. The research
includes the launch of 12 new projects,
continuation of five projects entering their second year, and three
Storm
Cat Career Development Awards.
EVALUATION OF A RAPID TEST FOR SALMONELLA
Dr. Paul Morley, Colorado State University – First Year (2 Year Grant)
Salmonella enterica is the most commonly reported cause of outbreaks of hospital–acquired infections in veterinary teaching hospitals and the most common cause of closure of equine hospitals. Congregating horses from multiple sources is associated with increased risks for spread of contagious disease such as Salmonella. Control of Salmonella is further complicated by the fact that both horses and environment can appear clean and still be contaminated with Salmonella.
Developing methods for testing that can be performed at veterinary clinics and performing objective comparisons
of Salmonella detection methodologies were recently identified as critical needs for infection control in equine populations by an international panel of infection control experts. Rapid and reliable testing methods for S. enterica
in environmental and fecal samples are considered essential for facilitating effective infection control in horse populations. Current detection methods typically require 48–96 hours and 24–72 hours from submission to reporting, respectively, in addition to time needed for transportation of samples to the laboratory.
Recently, commercial tests have been developed for use in food safety microbiology which may provide
a practical and useful alternative to traditional culture and polymerase chain reaction (PCR) methods when screening for Salmonella. These lateral flow immunoassays could be economically employed in point–of–care testing providing a 24 hour test result for fecal samples and 48 hour test results for environmental samples with reasonable sensitivity. This will allow more extensive yet less expensive use of screening to control Salmonella in veterinary settings. The Central Hypothesis for this work is: Commercially available test strips used in the food production industries can be adapted for use as a rapid, point–of– care test to detect Salmonella in horse feces or environmental samples with sensitivity that is equivalent to optimized culture or PCR testing. To address this central hypothesis we will identify an optimal culture technique for fecal cultures and use an established culture protocol for environmental samples. We will also test these samples with a validated commercial PCR test kit, and with the Reveal® 2.0 rapid test strip. We will use these test results to estimate the sensitivity and specificity of these tests using state–of–the art, best–practice epidemiological methods.
Gallium: An Alternative to Macrolides Against R. equi?
Dr. Noah Cohen, Texas A & M University – One Year
Pneumonia caused by Rhodococcus equi remains an important cause of disease and death in foals. Effective prevention for this disease is lacking. A vaccine remains elusive, despite decades of intensive efforts to develop one.
However, administering macrolides (the class of antibiotics that is the treatment of choice for R. equi) to all foal for prevention has been demonstrated to be effective at reducing the incidence of R. equi pneumonia; although this approach (known as chemoprophylaxis) is not uniformly effective. Moreover, chemoprophylaxis is likely to result in development of resistance to macrolides by R. equi, which is of grave concern.
The absence of effective methods to prevent R. equi pneumonia has led many veterinarians and farm managers to implement screening programs for early detection of R. equi–infected foals. The most widely used screening test is sequential ultrasound examinations of the lungs. The rationale for this screening is that the disease is slowly progressive such that clinical signs generally are not apparent until the disease is well advanced. By using screening tests, disease can be detected earlier in its course; in early stages of disease, treatment is expected to be more effective and shorter in duration.
A problem that arises with screening is that the apparent incidence of disease is increased because many foals that have lung ultrasound findings consistent with R. equi pneumomia would not progress to develop disease. The increased apparent incidence of disease results in more foals receiving macrolide antibiotics for treatment. Thus, screening – like chemoprophylaxis – results in increased pressure and opportunity for macrolide resistance to develop.
We propose a randomized, controlled clinical trial to evaluate whether gallium maltolate (GaM) is effective as an alternative to macrolides for treating foals with presumed R.equi pneumonia identified by ultrasound screening. GaM is a metal–based drug that can be given by mouth and is well absorbed from the intestinal tract of foals. GaM is effective against R. equi (including macrolide–resistant isolates) in the laboratory setting. Anecdotally, the investigators have used GaM to successfully treat foals with R. equi infections.
This study is important because it would help reduce the amount of macrolides being used at breeding farms, without eliminating the process of screening that permits earlier identification of foals that will develop R. equi pneumonia. This result will reduce the risk of development of macrolide resistance, which is important both for equine and human health, while helping to control a major health problem of foals.
DEVELOPMENT OF ALTERNATIVE MODELS TO STUDY EHM
Dr. Gisela Soboll Hussey, University of Michigan – First Year (2 Year Grant)
Equine Herpesvirus-1 (EHV-1) infection has resulted in devastating outbreaks of neurological disease caused by a Myeloencephalopathy, with a poorly understood pathogenesis. The impact of EHV-1 Myeloencephalopathy (EHM)
on equine health and industry is highlighted by a series of major outbreaks in North America over the past decade, including the largest outbreak ever in 2011. Despite the research community’s emphasis on EHM, a significant knowledge gap still limits our ability to prevent this devasting disease, and this is the focus of this proposal. Reasons for this knowledge gap include the fact that the naturally occurring disease remains relatively rare, and EHM can only be
experimentally reproduced in aged and immunosenescent horses which are unrepresentative of the naturally affected population.
The long-term goal of our research is to control the occurrence of EHM. To accomplish this goal, which is the objective of this proposal, is the development of equine models in which to study EHM pathogenesis and to determine the efficacy of preventive measures. The rationale of this proposal is based on powerful preliminary data showing that endothelial cell infection and pathology of the eye is a common event and that EHV-1 infection of the eye mirrors the disease seen in the CNS during EHM.
We predict that we will find evidence of similar infection of the CNS and identify markers of sub-clinical disease in CSF. Using cutting-edge mass spectrometry techniques, we have already identified a number of exciting candidate markers. There is good evidence in a number of studies in humans and other species, that infection and injury of the spinal cord or brain are commonly associated with specific biomarkers, and that these markers can be detected using spectrometry. The use of both the ocular model and biomarkers for studying EHM is a highly innovative approach that, if successful, will answer critical questions about the pathogenesis of EHM and provide practical and ethical models for studying vaccines and therapeutics for protection from the devastating outcomes of EHM.
The development of the proposed models would drastically change EHM research as it would provide the means to test future vaccines or therapeutics in a model that is directly applicable to natural conditions. Furthermore the proposed research might also provide new diagnostic tools that could be used in outbreak conditions to identify horses at risk for developing EHM.
FACTORS AFFECTING OMEPRAZOLE PHARMACOKINETICS IN HORSES
Dr. Paul Mills, University of Queensland, Australia – One Year
The horse’s stomach is a single chamber with two different linings. The top half is lined by a squamous mucosa
which is akin to our skin or the lining of our esophagus. Until recently the focus of research and clinical practice has been on ulcers in the upper half, and it is well recognized that they are primarily the result of increased acid exposure to an area unaccustomed to acid exposure. The bottom half of the stomach is lined by a glandular mucosa akin to the lining of our stomach and it is thought that ulcers in this area more closely resemble gastric ulceration in humans.
The architecture of the lining of the bottom half of the stomach is significantly more complex than that of the top half and the cause of ulcers in this area is believed to be related more to a failure of normal defense mechanism than increased acid exposure per se. Until recently little research has been performed on ulcers in the lower half of the stomach and treatment recommendations have simply mirrored those for the ulcers in the top half of the stomach.
The reasons for this are not currently understood, but given the simple nature of the lining of the top half of the stomach it is likely that the duration of acid suppression may be less than required for healing of the more complex lining of the bottom half. As such, the possibility exists once-daily administration is inadequate in the lower half.
Studies have suggested that the clearance of omeprazole in the horse is much more rapid than other species, so that acid suppression lasts a shorter time in those species (including man). However, accurate interpretation of how omeprazole behaves in the horse’s body is currently impossible. Recent improvements in analytical techniques mean that more accurate information is likely to be obtained with repetition of this basic work.
With the above in mind the study has several aims: 1) To document the basic behavior of omeprazole in the horse’s body. This includes determination of the absorption and elimination of the drug following intravenous and oral administration; 2) To document the effect of enteric coating (which is believed to improve absorption by protecting the omeprazole from acid in the stomach) on absorption following oral administration; 3) To document the effect of feeding on absorption following oral administration as early studies suggest that this may be major factor in the efficacy of the drug.
The long term objective of this project is to develop a model to study the behavior of omeprazole under various clinical conditions so that more specific treatment recommendations can be made to address ulcers in the bottom half of the stomach.
MOTOR RESPONSES IN EQUINE CERVICAL STENOTIC MYELOPATHY
Dr. Cody Alcott, Iowa State University College of Veterinary Medicine – One Year
Equine cervical vertebral stenotic myelopathy (CVSM) is a multifactorial compressive injury to the cervical spinal cord and adjacent nerve roots. Differentiating CVSM from infectious causes of spinal cord dysfunction or orthopedic disorders can pose a challenge to the equine practitioner. Premortem diagnoses have traditionally used a combination of clinical neurolocalization, survey radiography and myelography. Cervical radiographs, typically lateral projections alone, offer dorsoventral assessment of spinal canal narrowing when referenced to vertebral endplate diameter.
Single plane radiographic projections do not account for 3-dimensional changes of a tubular spinal canal and
lack the objective consistency to confidently diagnose CVSM unless compression is blatant. Myelography is performed to identify spinal cord compression and can be performed in various head positions in lateral recumbency.
Again, myelography evaluates dorsoventral spinal cord compression and fails to account for compression in other plans. When compared to histopathology of the spinal cord, the gold standard diagnosis of CVSM, the accuracy of both radiography and myelography rarely achieves more than 60% in most cases. Adjunct diagnostics have failed to enhance objective identification of CVSM. Computed tomography and MRI are promising diagnostics but as of yet have limited utility in adult horses due to size limitations. Functional assessment of the cervical spinal cord in horses with CVSM has not been described objectively, outside of histopathology, and is probably the most important aspect of spinal cord injury especially when prognosticating return to athletic function. Furthermore, the previously mentioned diagnostics lack the sensitivity to identify mild or subclinical disease, which is the most opportune time to intervene in horses with early CVSM.
Transcranial magnetic motor-evoked potentials (TMMEPs) objectively document the elapsed time of an electrical volley generated in the motor cortex (or extrapyramidal tracts) to distant muscle groups via motor conduction pathways. Electrophysiologic examination of spinal cord motor function in horses via TMMEP has been documented previously, but its clinical application in horses with CVSM has not been explored nor compared to histopathologic confirmation of spinal cord injury. Surgical vertebral stabilization surgery has been employed to halt the progression of spinal cord injury in horses with CVSM. Moderate improvement can be expected following surgery with some horses; however dramatic improvements have also been reported. What functional spinal cord changes occur in CVSM horses following surgery is unknown, in addition to clinical improvements as a result of true spinal cord repair or neurogenic compensation. Objective electrophysiologic assessment of spinal cord motor function will also prove essential when evaluating future therapeutic interventions.
DETECTION OF LAMENESS IN RACEHORSES AT THE GALLOP
Dr. Kevin Keegan, University of Missouri – One Year
This project addresses development of an objective method (i.e., using measurements performed by a calibrated instrument) for detection of obscure, subtle lameness in horses at the gallop with a relatively low cost and that can be used in the field will contribute for significant advancements in the understanding of the causes and mechanisms of lameness in the race horse. This new method will also be useful for studying the relevance of the findings of clinical examination as well as the effectiveness of current and new treatments, and of preventive prophylactic measures.
ACOUSTOELASTOGRAPHY TO MONITOR INJURED EQUINE TENDON
Dr. Sabrina Brounts, University of Wisconsin–Madison – First Year
The superficial digital flexor tendon (SDFT) is a commonly injured soft tissue structure in performance horses.
Injury of this structure is site–specific and commonly affects the mid–portion of the SDFT. Prognosis for return to full athletic function is guarded due to the fact that often horses are placed back into work to soon and re–injury of the tendon occurs. Therefore, it is important to be able to assess quantitatively the mechanical properties of tendons under load before the horse returns to full athletic use. At the University of Wisconsin a novel technique called “Acoustoelastography (AEG) was developed, which interrelates the ultrasound wave propagation to the local tissue biomechanical stiffness. Pathological diseased tendon has less stiffness than normal healthy tendon. AEG can assess this in real–time without knowing/recording tissue loads or performing extensive numerical analysis on images. The goals of this project are: To determine whether Acoustoelastography (AEG) can measure mechanical properties and strains non–invasively in abnormal equine tendons and secondly evaluate the healing of the equine superficial digital flexor tendon (SDFT) during recovery from tendon injury.
In this study, we will evaluate tendon stiffness in the SDFT that had an injury and therefore pathologic changes. This stiffness will be compared to the normal stiffness of a SDFT. We will then demonstrate secondly that the stiffness of a tendon changes during its healing process. Horses with injury to their SDFT will be followed for 6–12 months to show that stiffness increases as the tendon heals. We expect that this study will show that a simple non–invasive evaluation of tendon function is possible and is able to detect, monitor and help in the rehabilitation of tendon injury. This grant was selected by the board to receive the seventh annual Elastikon™ Equine Research Award.
EVALUATION OF BIOFILM FROM EQUINE UTERINE BACTERIA
Dr. Ryan Ferris, Colorado State University – One Year
Mares with fertility issues may have a chronic bacterial infection in their uterus that is resistant to traditional antibiotic therapy. Bacteria involved in chronic uterine infections may be capable of forming biofilms, a sugar–like matrix that coats bacterial colonies adherent to the wall of the uterus in a ‘protective blanket’. The biofilm matrix is able to provide protection from the natural uterine immune system by altering the movement and function of white blood cells, and preventing antibodies from binding to bacteria. In addition, biofilms confer resistance to antibiotic therapy by reducing the amount of drug that reach the bacteria and decreasing metabolism and replication of the bacteria so that antibiotics are not as effective. Ultimately, biofilms propagate a population of bacteria that are protected and resistant to antimicrobial agents. It has been proposed that biofilms play an important role in chronic endometritis and treatments designed to break down biofilms have been suggested. However, very little is known about the production of biofilm by bacteria recovered from infected mares. The goals of this proposal are to 1) determine the percentage of bacteria recovered from equine uterine cultures that produce biofilm 2) identify genes in bacteria associated with biofilm production, and 3) determine the efficacy of therapeutic agents used in horses and humans to break down or degrade biofilm.
MOLECULAR DETERMINANTS OF EHV-1 FUSION AND SPREAD
Dr. Arthur Frampton, University of North Carolina Wilmington – First Year (2 Year Grant)
Equine herpesvirus 1 (EHV-1) is the cause of significant illness in horses worldwide. The virus belongs to a family
of herpesviruses called the alphaherpesviridae, which includes the human viruses, herpes simplex virus 1 and 2
(HSV-1, HSV-2). While EHV-1 has many features that are similar to the human herpesviruses, such as structure and genetic makeup, there are also important differences between the equine and human viruses. These differences include the mechanism of transmission or spread of the viruses and the clinical symptoms that arise after infection. Horses become infected with EHV-1 after coming into contact with airborne droplets containing virus particles or through contact with infected surroundings such as contaminated bedding. Once infected, horses exhibit
clinical signs including respiratory distress, fever, lack of appetite, and other signs associated with a “common cold”.
While most horses recover from this infection with no long-lasting negative effects, some horses will experience serious complications resulting from EHV-1 infection. Two major complications that may arise include neurological problems including the disease equine herpesvirus myeloencephalopathy (EHM) and abortion in pregnant mares. These secondary conditions occur after the virus spreads from the upper respiratory tract to very sensitive sites such as the central nervous system (CNS) and endometrium (uterine cavity). Recently, there has been a significant increase in the number of neurologic cases caused by EHV-1 across the U.S. prompting the USDA to declare EHM
a potential emerging disease. In the late Spring/early Summer of 2011, there were 90 cases of EHM reported in 10 states and 13 horses succumbed to the disease [1]. Due to the increase in EHM cases it is critical that the underlying molecular mechanisms by which EHV-1 causes EHM be investigated so that appropriate therapeutic interventions can be developed and delivered. Although research is ongoing to identify why some horses develop these severe conditions while others recover without incident, much more information needs to be obtained in this area.
Previous work by other groups identified a mutation within the viral DNA polymerase enzyme that is correlated with EHM disease [2, 3, 10]. While this mutation does contribute to neurologic disease, other viral and host factors must also contribute to EHM as viruses that do not contain this mutation have been isolated from EHM horses and infection with some EHV-1 strains that do harbor this mutation do not lead to neurologic disease. For these reasons, studies aimed at identifying addditional neurovirulence factors are warranted.
Studies outlined in this proposal will be performed to investigate the interaction of neurologic and non-neurologic strains of Equine herpesvirus 1 (EHV-1) with cells in order to identify specific viral and cellular factors that contribute to efficient fusion and cell to cell spread of EHV-1. Preliminary data obtained from our lab showed that the MHC-I receptor is used by a non-neurologic EHV-1 strain (RacL11) to enter and spread from one cell to the next. Results obtained from the experiments outlined in Aim #1 will reveal whether MHC-I is similarly used by neurologic EHV-1 strains for entry and spread and will also aim to identify additional cellular factors that contribute to disease outcome. In addition to identifying the key cellular factors, the essential set of viral glycoproteins that are needed to mediate fusion with cellular membranes will be determined in Aim #2. Once these key fusogenic glycoproteins are identified, we will determine whether specific mutations in any of the glycoproteins isolated from neurologic strains are responsible for their ability to increase fusion as this property is positively correlated with virulence. Finally, in Aim #3 the contribution
of accessory glycoproteins including glycoprotein I and E to cell to cell spread will be evaluated.
EFFECT OF CYP2D GENETIC POLYMORPHISMS ON DRUG METABOLISM
Dr. Heather Knych, University of California, Davis – One Year
Establishing an appropriate treatment regimen for a drug, in light of the large degree of individual variability between horses provides a constant challenge to veterinarians and necessitates further study into the reasons for the varying responses. Similar to that observed in horses, a comparable degree of individual variability in response to drugs has been noted in humans. One documented reason for these differences is variability in the activity of drug metabolizing genes, most notably, CYP2D6. Based on differences in the genetic code, individuals are classified as poor, extensive and ultra rapid metabolizers, which describes their ability to metabolize a drug and ultimately their response. A similar enzyme has been discovered in horses (CYP2D50) and it has been postulated that differences in the genetic code of this enzyme may help explain some of the differences observed in horses.
In previous studies conducted by our laboratory, we have begun to characterize horses with respect to CYP2D50.
In these studies, a number of alterations in the CYP2D50 gene were identified, which may alter the function of this enzyme. Furthermore, we administered the drug tramadol, which is metabolized by the CYP2D50 enzyme, to and correlated the results of the genetic analysis with the information gathered from the tramadol administration studies. Although, the sample size for this study was very small, and additional studies are necessary to confirm these results, the data seems to support reports of a distribution similar to humans (poor, extensive and ultra rapid metabolizer), which may play a role in differing response to drugs (toxicity and subtherapeutic responses) between horses.
In the proposed study, blood samples will be obtained from an additional 50 horses and the genetic code for the enzyme CYP2D50 determined. The gene will be analyzed for differences that have the potential to affect activity. Twelve horses will be selected based on results of the genetic anlaysis, for a drug administration study utilizing three drugs (tramadol, dextromethorphan and debrisoquine) that are metabolized by the CYP2D gene. In addition, nine horses, previously studied will be administered dextromethorphan and debrisoquine. Analysis, similar to that previously done in humans, will be conducted in an attempt to
correlate the genetic code with response to drug administration.
SERUM BIOMARKERS FOR EQUINE LAMINITIS
Dr. Hannah Galantino–Homer, University of Pennsylvania – First Year (2 Year Grant)
The goal of this study is to improve the understanding and early diagnosis of equine laminitis. Equine laminitis is a disease that affects the suspension of the bone of the foot, and hence the weight of the horse, to the hoof capsule via the interdigitating lamellae of the hoof and underlying connective tissue. Laminitis causes failure of digital suspension resulting in excruciating pain and often resulting in humane destruction of the horse. Our previous studies, using archived samples from two experimental models of laminitis, detected molecular changes that are helping us understand the steps preceding full-blown laminitis. In human diseases, molecular changes in the affected tissue are often reflected in molecular changes in the blood. These “disease markers” can then be used to diagnose early stages of a disease, when therapies are the most effective. Our preliminary studies have determined that one of our potential markers is elevated in blood samples from an experimental model of laminitis and from horses with laminitis associated with a non-weight-bearing orthopedic injury (supporting limb laminitis). The goal of the proposed study is to identify at least three serum markers that would be useful for diagnosing the early, inapparent or “developmental” phase of laminitis and to detect the resulting tissue damage and the body’s immune response to that damage.
Based on our earlier studies, we will investigate blood levels of specific proteins using samples from horses without laminitis, horses in the early stage of the disease prior to lameness, and horses with overt laminitis. The studies will involve methods for the identification and quantification of proteins in tissue and blood samples and for the detection of specific classes of antibodies involved in the immune response. Positive results from this study will then be used to develop diagnostic tests to detect incipient laminitis in horses that are believed to be at risk of developing the disease, such as horses with a prior history of laminitis, severe orthopedic injuries, colic, obesity, or horses that have ingested excess grain, and to assess lamellar tissue damage. New technology that allows the “multiplexing” of assays for several markers into a single assay will be used to generate an assay for lamellar tissue damage.
THE INTERACTION BETWEEN ANTHELMINTIC TREATMENT AND VACCI
Dr. Martin Nielsen, University of Kentucky; Gluck Equine Research Center – One Year
Both deworming and vaccination are carried out on a routine basis in all managed equine establishments, and it is not unusual to deworm and vaccinate horses on the same day. Until recently, this was considered to be an unproblematic approach, but recent findings have raised concerns about possible interactions between deworming and vaccination. Deworming causes a mild and transient inflammatory reaction in the horse, which appear to depend on the type of dewormer used. This has been found to cause disease in newly dewormed horses, but usually the inflammatory reaction is mild with no apparent symptoms. However, it is unknown whether this reaction can possibly affect the result of vaccination. Our hypothesis is that deworming causes an inflammatory reaction that affects vaccination. This one year study will evaluate this by exposing three groups of ponies (8 per group) to three different types of vaccine administered at the same time (one with adjuvant, one being a live virus vaccine, and one with no adjuvant). Two of the groups will be dewormed with two different dewormers (pyrantel pamoate and ivermectin) at the time of vaccination. This allows us to measure the effectiveness of the deworming, the antibody response to the vaccine, and the inflammatory reaction to vaccination with and without the accompanying deworming. Ponies will be followed for a total of 60 days with collection of fecal and blood samples to evaluate deworming effectiveness, inflammatory response and generation of vaccine-specific antibody levels. The study will generate useful information about the interaction between deworming and vaccination and the possible influence on vaccination effects. In addition, the study allows evaluation of possible differences between two types of dewormer in their effect upon vaccination responses.
LIPOSOMAL GENTAMICIN FOR THE TREATMENT OF R. EQUI
Dr. Steve Giguere, University of Georgia – Second Year
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– Second Year
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 source 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.
LAMINAR SIGNALING IN SUPPORTING-LIMB LAMINITIS
Dr. James Belknap, The Ohio State University–Second Year
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.
STEM CELL HOMING AFTER IV REGIONAL LIMB PERFUSION
Dr. Alan Nixon, Cornell University– Second Year
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."
TOWARDS A TREATMENT FOR TESTICULAR DEGENERATION
Dr. Regina Turner, University of Pennsylvania– Second Year
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
Three candidates have been selected to receive the Seventh Annual Storm Cat Career Development Award.
They are:
Erin McConachie, University of Georgia
-CARDIOVASCULAR FUNCTION IN HORSES WITH COLIC
This study is a first of its kind for colic in horses using measurable cardiac parameters to identify clinically relevant risk factors associated with wide spread organ damage in surgical colics in an effort to determine the most effective screening techniques; future care can be directed at appropriate monitoring and therapeutics to improve both outcome and long term survival.
Daniel Youngstrom, Marion duPont-Scott Equine Medical Center
-OPTIMIZATION OF TENDON REGENERATION
This study deals with optimizing tendon regeneration using a unique bio-reactor method of stem cell maturation and differentiation which mimics fetal development of stem cells. This allows the investigators to produce cells primed to become tendon specific cells as opposed to the naive in character cells now used thus maximizing the efficiency of future stem cell therapy in tendon regeneration.
Brandy Burgess, Colorado State University
- EPIDEMIOLOGY OF SALMONELLA IN EQUINE HOSPITALS
This project addresses one of the most serious problems faced in equine hospitals, Salmonella enterica outbreaks. The principal goal of this investigation is to gain a better understanding of the contributing factors to animal shedding, environmental contamination and transmission risks related to endemic S. enterica. The model produced from this will allow animal population managers to practice evidence based infection prevention strategies clearly motivated by proven epidemiology.
The Storm Cat Career Development Award, inaugurated in 2006, is a $15,000 grant designed as an early boost to an individual considering a career in equine research. It has been underwritten annually by Mrs. Lucy Young Hamilton, a Grayson-Jockey Club Research Foundation board member whose family stood the retired champion stallion Storm Cat at Overbrook Farm.
“The committee who selects the Storm Cat recipients described how difficult it was this year to select one over two other exceptional candidates,” said Grayson-Jockey Club Research Foundation President Edward L. Bowen. “Since Storm Cat is now 30 years old, our chairman, Dell Hancock, suggested that we fund all three — one for each decade of the stallion’s life — on this one occasion. Therefore, Lucy Young Hamilton will fund one of them and our foundation will fund the other two and we will be helping three young researchers this year.”
