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| Grayson-Jockey Club Research Foundation will fund 19 projects
in 2010, totaling $889,697. The research includes the launch of 15 new projects,
continuation of four projects entering their second year, and the Storm
Cat Career Development Award. |
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| Antiviral Drugs To Combat Equine Herpes Virus-1
Infection |
| Dr. Arthur Frampton, University of North Carolina-Wilmington.
Second year |
|
| Equine herpes virus-1 continues to be a major problem, which can
result in paralysis and, in the case of pregnant mares, abortion.
While a number of research projects on EHV-1 are ongoing, there is
not an effective vaccine which is long lasting, so horses are subjected
to repeated vaccination. This proposal seeks a solution other than
vaccination, i. e., that a better approach might be surveillance and
health monitoring coupled with antiviral drugs after EHV-1 infection.
This approach would seek to lessen significantly the possibility of
an infected horse becoming paralyzed or aborting. Many horses recover
from EHV-1, and the treatment protocol suggested here could be expected
to improve that rate. |
| Prevention Of Equine Herpes Virus-1 Myseloencephalist
By Delayed Therapy |
| Dr. Lara Maxwell, Oklahoma State University. Second
year |
|
| This study will seek to determine whether drug therapy can be effective
if applied in barns where Equine Herpes Virus-1 has gone unidentified
until horses are in the latter stages of infections. At that stage
of infection, neurological disease can be expected to develop within
a few days. This research team has found that the antiviral drug valacyclovir
is effective if administered early in the course of the infection,
and this new project could be important in protecting horses from
developing crippling disease and also reducing the contagious period
of the infection. |
| Developing Equine Bone Morphogenetic Protein
For Cartlage And Bone Repair |
| Dr. Matthew Stewart, University of Illinois at
Urbana Champagne. Second year |
|
| Bone morphogenetic protein 2 has been effective in human medicine
for fracture repair and spinal fusions. This project seeks to develop
an equine BMP-2 gene therapeutic reagent and demonstrate that it can
be applied to stimulate accelerated bone formation and cartilage repair.
In our most recent newsletter, Dr. Mark Markel noted that “there
are currently no groups producing sufficient quantities of equine
BMP-2 necessary for clinical applications.” The above project
could help fill that need. |
| Race Surface Optimization for Fetlock Injury
Prevention (II) |
| Drs. Sue Stover & Mont Hubbard, University
of California-Davis, One Year |
|
| This is the logical extension of a one-year grant funded last year
in which the use of a 4 X 4 foot box was utilized to duplicate the
make-up of race track surfaces. The question of the first project
was whether this process could be validated, and early indications
are that it was a success. The next step continues the process. The
composite review from the Research Advisory Committee included the
comment that continuing along this path could eventually “allow
evaluation of literally hundreds of racetrack surface characteristics
to better optimize their material properties.” |
| Ethyl Pyruvate and Endotoxemia in Horses |
| Dr. Sue Holcombe, Michigan State University, One
Year |
|
| Endotoxemia is a common cause of death in serious equine conditions
such as colitis, strangulating intestinal obstructions, and septicemia.
Available treatments are not consistently successful, and finding
a clinically useful treatment, without side effects, remains an important
goal. That is the basis for this project, which will test whether
ethyl pyruvate is a useful medication. It has been shown to ameliorate
intestinal, cardiac, and other conditions in humans and other species.
In humans, it has been found to be effective in critical illness even
after the problem has become acute. Further, it has already been shown
to be safe for horses. The investigator hopes to demonstrate that
ethyl pyruvate treatment will be more effective than flunixin meglumine,
and it would also be considerably less expensive. |
| In Vivo Gene Transfer for the Treatment of Laminitis |
| Dr. Dean Richardson, University of Pennsylvania,
First Year |
|
| This project seeks to develop a gene therapy approach to prevent
laminitis in the contralateral hoof when a horse is being treated
for a musculoskeletal injury. This, of course, was what eventually
ended the efforts to save Barbaro and is a frequent threat to horses
with hoof and leg injuries. The well known research team already has
compelling preliminary data which encourages the hypothesis that use
of recombinant adeno-associated viruses can be used as vectors to
deliver a therapeutic gene (TMP-3) to the lamellar tissues. This is
meant to inhibit the damage to the epidermal laminae without disrupting
the normal hoof structure. |
| Endotoxemia as a Predisposing Factor for Laminitis |
| Dr. Nicholas Frank, University of Tennessee, One
Year |
|
| There exists considerable circumstantial evidence that there is
a relationship between endotoxin and onset of laminitis. This project
seeks to verify that causal relationship and, if it successfully does
so, would also verify that use of anti-inflammatories has a valid
scientific basis. |
| Factors Associated with Success and Failure
of Early Pregnancy |
| Dr. Keith Betteridge, University of Guelph, First
Year |
|
| Pregnancy loss during the third week of gestation is a major problem
in horses. Reviewers regarded it likely that this project will provide
greater understanding of the interaction of the conceptus and the
endometrium at that time of gestation. The probable understanding
of proteins associated with early pregnancy loss will help in understanding
mechanisms involved in both successful and failed pregnancies, and
suggest possible methods of therapy. The techniques employed will
include comparison of the transcriptomes of endometrium and trophoblast
in successful and unsuccessful pregnancies, characterizing the influences
of prostaglandin, and identifying factors produced by the fetus that
correlate with the processes of its immobilization. The researchers
will examine gene expression of associated proteins, etc., in normal
and failed pregnancies to search for markers of early embryonic loss. |
| Mechanisms of Pulmonary Vein Remodeling in
EIPH |
| Dr. Fred Derksen, Michigan State University, First
Year |
|
| This is the next step in a sequence of projects undertaken by Dr.
Derksen, some funded by the Foundation. This research team has discovered
scarring around blood vessels in the lungs of horses affected with
Exercise Induced Pulmonary Hemorrhage (EIPH). It is believed that
the scarring obstructs the veins, causing blood to back up in the
lung and rupture its fragile small \blood vessels. The main goal of
this next study is to determine why the scarring occurs, by studying
changes in molecules in vein walls that occur in response to exercise,
both in non-EIPH horses and EIPH horses. Understanding EIPH pathology
in general and the vein scarring in particular is described as necessary
before the ultimate goal of prevention or effective treatment could
be achieved. |
| Systemic Effects of Analgesic Combinations
in Horses |
| Dr. Chris Sanchez, University of Florida, First
Year |
|
| Management of pain is a key element in veterinary care of horses,
especially those with colic or lameness. In addition to the humane
urge to protect the animal from pain, there is a case management element
in that the pain is often accompanied by severe inflammation that
can lead to organ failure and founder. Many pain killers, however,
have negative side effects including stomach ulcers, diarrhea, and
kidney failure, so that seeking better pain killers is an important
subject for research. This project will test lidocaine, ketamine,
and butrophanol, individually, and in combinations not only for their
pain killing properties but to verify that they have no adverse side
effects on behavior, heart rate, respiratory rate, gastrointestinal
function, or the immune system. The study is predicated on the belief
that none of those ill effects will be manifested. |
| Rapid PCR Diagnosis of Equine Botulism Types
A, B, and C |
| Dr. Raymond Sweeney, University of Pennsylvania,
First Year |
|
| Botulism occurs throughout North America and in any given year some
cases can be expected. When it does strike, it can spread quickly,
and last year one outbreak caused the death of 100 horses. Surviving
botulism depends on rapid diagnosis, followed by antitoxin administration.
One of the difficulties in managing botulism outbreaks is that the
traditional diagnostic test requires two to three weeks. The goal
here is to develop a test that can verify the disease much more rapidly.
The Foundation funded this research team previously, and they have
made major progress in developing a polymerase chain reaction (PCR)
test for botulism type B. This work will continue that effort and
extend to types A and C. The research capitalizes on recent progress
in detection of botulism in humans, driven by the disease’s
potential as a bioterrorism threat. |
| Clinical Administration of Doxycycline for
Arthritis |
| Dr. Lisa Fortier, Cornell University, First Year
|
|
Arthritis is a common problem in horses. Treatments are divided
between those that alleviate pain and those that preserve joint cartilage,
but there is need for additional, easily administered oral treatments
to halt the progression of arthritis. Doxycycline belongs to the tetracycline
family of antibiotics and is typically used in hoses to treat Lyme
disease. It is believed to have potential in alleviating arthritis
because it is a potent inhibitor of enzymes called matrix metalloproteinases
(MMPs). MMPs are responsible for degrading cartilage in joints, leading
to arthritis. The MMP-inhibiting effects of doxycycline can be achieved
at concentrations far lower than those required to kill bacteria.
One aspect of this study will be to determine a minimal dosing level
to treat arthritis, one that is not antibacterial and thus would have
not potential for contributing to drug-resistant bacteria. It is anticipated
that if doxycycline is verified as useful treatment against arthritis,
it can be easily administered by lay persons.
|
| Toxins TCD A & B of Clostridium Difficile
for Horse Immunization |
| Dr. Sergey Artiushin, University of Kentucky, One
Year |
|
| Clostridium difficile is a bacteria that multiplies in the intestines
of horses and other mammals when normal bacterial flora is poorly
developed or becomes disrupted. Two very large and potent toxins are
released by Clostridium difficile, causing massive damage to the intestinal
lining. The resulting enterocolitis is an important component of the
neonatal diarrhea complex. There currently is no vaccine, and treatment
is expensive. This project seeks to generate antibodies in the horse
to the parts of each toxin that bind to intestinal cells and thus
block entry of the toxin. The work will involve cloning of polypetides
of toxins A and B, using recombinant DNA technology. Success should
lead to a vaccine that could be administered to mares two months before
foaling. The vaccine would provide colostral antibodies to the newborn
foal. The approach is similar to that already in use to generate colostral
antibodies to a different Clostridium- connected toxin that causes
colitis in newborn foals. |
| Track Banking and the Asymmetry of Hoof Loading |
| Dr. Jeffrey Thomason, University of Guelph, One
Year |
|
This grant was selected by the board to receive the fourth annual
Elastikon™ Equine Research Award. With every stride at racing
speed, forces acting on the legs reach as high as two to three times
the horse’s body weight. Avoiding any increased loading is intuitively
regarded as beneficial in preventing injury. It is believed in theory
that having no banking on the turns or too-low banking can increase
the forces, but little scientific work on banking has been done since
Swedish studies on Standardbred horses in the 1970s. This study aims
to refocuses attention on developing insight into the effects of different
banking, by use of strain gauges. Additionally, the study will address
the widespread practice of racing and training almost exclusively
counter-clockwise in North America. Horses will be exercised in both
directions and measurements will be recorded as to strains on different
parts of the hoof in both directions.
|
| Orthopedic and Genetic Roles in Wobbler Syndrome |
| Dr. James MacLeod, University of Kentucky, First
Year |
|
| Wobbler Syndrome carries a guarded to poor prognosis, and many afflicted
horses are not good candidates for vertebral fusion and have to be
euthanized. The focus of this project will be to examine the role
of abnormal bone and cartilage formation in the neck vertebrae, and
to identify regions of DNA and, potentially, even specific genes that
are involved in Wobbler Syndrome. Technology will include three-dimensional
X ray, Magnetic Resonance Imaging, and DNA isolation. Variation in
the DNA nucleotide sequence of more than 54,000 positions across the
genome will be compared between horses afflicted and control-group
horses. This study is intended to add to existing understanding of
the cause and progression of Wobbler Syndrome and lead to improved
management and therapeutic practices. |
| Molecular Characterization of Neurovirulent
Equine Herpevirus-1 Strains |
| Dr. Udeni Balasuriya, University of Kentucky, First
Year |
|
| The increased incidence of the neurologic form of Equine Herpevirus-1
have caused highly publicized problems at race tracks, farms, and
other equine centers in recent years. The Foundation has supported
several projects on EHV-1, and this lab has discovered there are more
types of mutations than were previously thought, which have impact
on the prevalence of the neurologic strain of the disease. Further
complicating the issue is the discovery that some horses showed the
neurologic signs but did not have the predicted mutated forms of the
virus. This project will attempt to identify further additional reputed
neurovirulence determinants of EHV-1 by sequencing genes essential
for replication. The researchers will utilize the unique situation
at the University of Kentucky, where an extensive collection of EHV-1
isolates has been collected over many years. |
| Pharmacokinetics/Pharmacodynamics of Quinapril
in Horses |
| Dr. Jennifer Davids, North Carolina State University,
One Year |
|
| Antigen converting enzyme (ACE) inhibitors are frequently used in
human medicine and small animal veterinary medicine to treat heart
failure, chronic renal disease, and high blood pressure. One ACE inhibitor,
enalapril, has been studied in horses but found ineffective when given
orally. (Oral formulation is important because horses need to stay
on the drug for a prolonged period.) This project will test whether
another ACE inhibitor, Quinapril, is effectively absorbed by the horse’s
gastrointestinal tract. It has been shown to improve heart function
of horses with valvular disease and atrial fibrillation, but is not
yet widely used in horses because the absorption and pharmacological
effects in the species have not yet been adequately studied. This
project is aimed at answering that question and, if the results are
positive, to calculate the appropriate dose to achieve beneficial
effect. The researchers further raise the suggestion that Quinapril
might also prove to be beneficial in the treatment of laminitis and
heaves. |
| Equine Bone Regeneration with Adult Stem Cells |
| Dr. Mandi Lopez, Louisiana State University, First
Year |
|
| Adult stem cells in recent years have been the subjects of research
to determine their potential to treat injuries in horses. Bone repair
is one aspect which is being investigated. It requires about 70 million
adult stem cells to repair a single cubic centimeter of bone. Only
two types of tissues in mammals have been shown to have the potential
to provide that many stem cells, i. e., adipose (fat) and bone marrow.
The laboratory of this researcher has found that stem cells from both
sources indicate the ability to form bone in cell experiments. Comparisons
on the bone-forming abilities of fat-derived and bone-marrow-derived
stem cells have not been done conclusively, and this project will
address that important next question. The researchers believe that
“results from this study will significantly advance treatment
of broken bones in the horse.” |
| Storm Cat Career Development Award |
"Temporal Analysis of Megenchymal Progenitor Cells"
Dr. Catherine H. (Radcliffe) Hackett, Cornell University. One year,
$15,000
The Fifth Annual Storm Cat Career Development Award recipient is
Catherine H. (Radcliffe) Hackett, a post-doctoral fellow from Cornell
University. Dr. Hackett will be working with Dr. Lisa Fortier and
Dr. Julia Flaminio.
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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