Stem Cell Treatment Of Suspensory Desmitis
Robert K. Schneider from Washington State University
Injury to the proximal suspensory ligament of the hindlimb is a common cause of lameness in many equine athletes including Thoroughbred race horses. Depending on the severity of injury to this ligament, horses can be lost from competition for a minimum of 6-8 months, or injury can result in the end of the horse’s performance career. An effective treatment that allows a high percentage of horses to return to use does not currently exist. New treatments are needed to give these horses a better chance to return to performance and decrease the likelihood of reoccurrence of the injury. (back to top)
Gene Therapy For The Treatment Of Laminitis
Dean W. Richardson from University of Pennsylvania
Laminitis is unquestionably one of the most devastating diseases of the horse. It affects all breeds of horses and results in intense suffering for horses afflicted with its most severe forms. The causes and mechanisms of laminitis are very complex but the final common result of laminitis is that there is separation of the coffin bone from the hoof wall and often unmanageable pain. Laminitis frequently will end a horse’s competitive career and many horses are euthanized because of the persistent pain. There continues to be advances in understanding the underlying mechanisms of laminitis in horses. Most modern medical research eventually yields answers about diseases on a molecular level. As our understanding improves, more treatments and, most importantly, prevention will involve molecular approaches. Gene therapy is unquestionably one of the most promising general means of treating or preventing disease at a molecular level. The approach being studied here is something that would already be practical as a prophylactic treatment in horses being treated for a major musculoskeletal injury. (back to top)
Gene Therapy to Prevent Osteoarthritis
Laurie Goodrich from Colorado State University
Currently, attempts to treat and prevent osteoarthritis in the horse are palliative at best. The lack of ability to control inflammation in the joint has resulted in widespread destruction and suffering in the equine population, especially sport horses. If a gene therapy approach to control inflammation could result in a safe and effective method to actually prevent and actually inflammation, the consequences would result in the reduction of horses that suffer from the chronic pain of osteoarthritis and this would greatly lessen the number of horses whose promising careers are shortened due to ongoing inflammation and joint degeneration.
Our preliminary research in utilizing AAVIRAP gene therapy techniques suggests cells of joints are easily reprogrammed to produce beneficial proteins. The results of this project will define the most appropriate dose of AAVIRAP construct that will result in effective levels and answer the question of whether we can prevent osteoarthritis in the horse using this approach. (back to top)
Investigation Of Cell And Growth-Factor Dependent Tenogenesis
Martin Vidal from University of California- Davis
Tendon and ligament injuries are painful and debilitating diseases and are one of the most important equine orthopedic injuries related to the loss of use and euthanasia. The inadequate healing process of tendons results in mechanically inferior scar tissue formation and re-injury rates ranging from 23 to 67%. Our preliminary data suggest that there may be better cell types than stem cells from bone marrow and fat for the repair of tendons and ligaments. This work has the potential to change the face of cell- and growth factor-based therapy for tendons and ligaments in equine regenerative medicine and is expected to provide a basis for further characterization and improvement of tendon and ligament tissue healing.(back to top)
Generation Of Equine iPS Cells For Regenerative Therapy Of Tendonitis
Lisa Fortier from Cornell University
Tendonitis is a career-threatening injury amongst equine athletes. Despite recent advances in the diagnosis and treatment of tendon injuries, many of the injuries are slow to heal and rarely regain their original strength, leading to a high rate of re-injury. For these reasons, stem cell based therapies aimed at tendon regeneration continue to be investigated. While multipotent adult bone marrow derived mesenchymal stem cells (MSCs) have been shown to improve the structural aspects of equine tendon healing, tendons treated with these cells appear to have very limited regenerative ability. Pluripotent stem cells such as embryonic stem (ES) cells in theory have the greatest potential for tendon regeneration, but their use in regenerative medicine is limited due to the potential issues of immune rejection and disease transmission.
The broad objective of 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 pluripotent 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. The long term hypothesis, beyond the scope of this proposal, is that equine iPS cells will enhance tendon regeneration when applied autogenously in an equine model of tendonitis. If this hypothesis turns out to be true, then iPS cells would dramatically accelerate both the quality and rate of tendon healing, preventing re-injury and preserving athlethic function. In addition, 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. (back to top)
Stem Cell Homing After IV Regional Limb Perfusion
Alan Nixon from Cornell University
Presently, joint and tendon diseases are the leading causes of retirement in performance horses, and treatment costs have escalated without significant and verified new treatments. Direct injection of cultured stem cells derived from each individual horse has had variable success in treating musculoskeletal disease, with better anecdotal results in tendon and ligament compared to bone and joint. More can be done, including pre-differentiation, gene-directed lineage targeting, and more efficient delivery. This proposal examines delivery by local vein injection to "back-flow" to bowed tendon and other disease conditions such as founder or traumatic arthritis. Injection to the supply vessels uses a natural conduit to the disease core, where cells leak to damaged areas in increasing numbers depending on the extent of the injury. Transplanted cells then exert normalizing and restorative effects that may avert the debilitating and occasionally life threatening sequelae of tendon breakdown, weight-bearing founder, or arthritis. 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. This study will map cell distribution in the tendons, ligaments, and joints of the forelimb after direct venous injection. This route would avoid costly surgical and invasive direct injection techniques to joints or bowed tendons, and establish the changes in cell repopulation in damaged tissues depending on extent of injury. Ultimately, we hope to return horses with possible career-ending tendon and joint injuries back to being competitive athletes.(back to top)
Cryotherapy (Icing) for Laminitis – How Does It Work?
James K. Belknap from The Ohio State University
Laminitis is a crippling disease that, due to the many common diseases that predispose to laminitis, adversely affects the entire equine industry and all breeds of horses. Equine laminitis is reported to cause an annual monetary loss of $13 million; up to 0.8 % of horses in the U.S. have been reported to be suffering from laminitis at any given time. The septic causes of laminitis addressed in this study affect most aspects of the thoroughbred industry and has resulted in either chronic lameness or, in the more severe cases, humane euthanasia of broodmares, breeding stallions, and racehorses. In addition to the financial toll, the disease takes a great emotional toll on horse owners due to the severity of lameness that commonly occurs in these animals.
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Seeking Causes for Laminitis
James K. Belknap from University of Tennessee
Laminitis is a painful disease that can end the career of a horse and may even lead to euthanasia. This disease indiscriminately affects all horses, from the most expensive racehorse to the backyard pony with little financial value. Losing a horse to laminitis can have a significant financial and emotional impact on the horse owner. Laminitis is a particularly devastating disease because treatment is largely supportive after lameness develops and hoof structures become damaged. It is therefore of utmost importance that we develop new strategies for preventing laminitis and this work must begin with identifying predisposing factors for this disease. Horses develop laminitis in conjunction with intestinal diseases such as colic and diarrhea, indicating that these conditions predispose horses to laminitis. It is therefore our hypothesis that systemic inflammation predisposes horses to laminitis. We hope to provide evidence of this link, which would support the use of anti-inflammatory drugs to prevent laminitis. If this link exists, other treatments for systemic inflammation may be developed in the future that will prevent laminitis and directly benefit the equine industry.
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Cryotherapy (Icing) for Laminitis – When to Use It
James K. Belknap from The Ohio State University
Laminitis is a crippling disease process that affects horses of all breeds, ages and uses. Laminitis has a profound impact on the equine industry both from a financial standpoint (with costs estimated at $13 million annually) and also from an animal welfare and emotional standpoint. A recent study reported that 13% of all horse operations in the United States had a case of laminitis in the previous year and 4.7% of these died or were euthanized. Equine laminitis has been listed as a priority for research funding not only by the Grayson Foundation, but also other major equine research foundations/funding agencies and the world’s largest professional organization dedicated to equine veterinary medicine, the American Association of Equine Practitioners (AAEP). By discovering therapies that effectively ameliorate laminitis, we can profoundly improve horse welfare and reduce the impact of this devastating disease on the entire equine industry.
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Supporting Limb Laminitis: What causes laminitis in the foot of a horse that is very lame in the opposite leg?
Andrew van Eps from The University of Queensland, Australia
Laminitis is a crippling disease that causes great morbidity and mortality. Supporting limb laminitis is perhaps the most familiar form of the disease to racing industry and general public, being the condition that led to the demise of Kentucky Derby winner Barbaro, in 2007. This highlighted the fact that, despite great advances in the treatment of even the most catastrophic limb fractures and infections in horses, supporting limb laminitis remains the major cause of treatment failure in these cases. An effective preventative strategy would be a significant step forward for the welfare of horses and for the horse industry.
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More Studies on Supporting Limb Laminitis
James K. Belknap from The Ohio State University
A recent USDA study reported that approximately 1% of all horses in the USA suffer from laminitis at any given time, and that approximately 5% of these animals die or are euthanized on an annual basis. Importantly, many others remained crippled. Due to both its devastating nature and the lack of effective therapies, equine laminitis has been listed as a priority for research funding not only by the Grayson Foundation, but also by the USDA, the Morris Animal Foundation and the American Association of Equine Practitioners. Supporting limb laminitis (SLL) is particularly devastating as a recent report indicates that greater than 50% of the cases are euthanized. SLL most commonly occurs in animals which are suffering from a joint (most commonly infection) or orthopedic condition (commonly a postoperative repair for a fracture or breakdown injury) that causes the animal to bear excessive weight on the opposite limb which succumbs to SLL. These animals are usually hospitalized, and being treated aggressively for their original disease process; as these are the types of therapies that can be extremely expensive, SLL is commonly occurring in a more valuable animal which warrants the expense of the initial treatment; this disease process is particularly important to the Thoroughbred racing industry as the fracture or breakdown injuries (e.g. Barbaro). There are currently no known effective therapies for SLL, adding to the frustration to the veterinarian, trainer and owner. It is imperative that basic research be funded addressing this unique, particularly devastating form of laminitis.
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Developing Better Tools To Study Immunity To Equine Herpes
Paul Lunn from Colorado State University
Equine Herpesvirus-1 infection causes enormous suffering in horses and extensive economic losses through frequent outbreaks of a range of diseases including epidemic respiratory disease, abortion, neonatal foal death, myeloencephalopathy, and chorioretinopathy. In the Thoroughbred industry, EHV-1 infection has at least three effects. Firstly, the clinical signs of respiratory disease in racing Thoroughbreds are more severe in younger horses, leading to frustrating delays in their athletic training program for lucrative “classic” races. Secondly, abortion occurs during the second half of pregnancy, causing enormous economic loss and with obvious equine welfare implications. Thirdly, outbreaks of neurological disease and abortion not only have welfare implications for the individual animals but can also lead to movement restrictions, thereby disrupting breeding or training schedules and causing management difficulties at racetracks and pre-training centers. During the past 3 years there has been a considerable increase in the reporting of outbreaks of neurological disease in North America and in Europe. The impact of EHV-1 infection, both real and as perceived by the industry and public may never have been higher.
It is imperative to develop better tools to study immune responses to EHV-1 if we are able to develop and test effective vaccines and understand how best to control disease due to EHV-1. The best available technology for this purpose is tetramers, and we are now ideally placed to synthesize these powerful tools. We are committed to sharing these reagents widely with other EHV-1 Researchers, which will facilitate EHV-1 research throughout the equine scientific community.
(back to top)
Studying A Drug To Protect Horses And To Limit The Contagious Period For Equine Herpes
Lara Maxwell from Oklahoma State University
The EHV-1 virus seems to cause more disease in adult horses now than it did in the past. This may be due to a change in the virus that has resulted in severe neurological disease in even well-vaccinated horses. The resulting outbreaks of EHV-1 have had a considerable impact on the U.S. racing industry, causing quarantines of racetracks at numerous U.S. tracks. The quarantines have been particularly problematic to horse that travel, due to subsequent restrictions on horse transport. The proposed study was designed to test whether drug therapy would be effective in a barn where a horse develops a fever due to EHV-1 infection and its stall mates are in the process of being exposed to the virus. These findings have the potential to be enormously important to the racing industry, because effective drugs would protect horses from crippling disease and limit the contagious period of virus infection.
(back to top)
The Development Of A Model To Study Equine Herpes Infection Which Will Significantly Influence Therapies And Vaccination Schedules Or Vaccine Development
Lutz Goehring from Colorado State University
The development of a model to study Equine Herpes infection which will significantly influence therapies and vaccination schedules or vaccine development.The neurological form of an Equine Herpesvirus-1 infection is an enormous and potentially growing threat to the equine industry- it is not only because horses with irreversible disease have to be euthanized, it is because of the infectious nature of EHV-12 that Thoroughbred races and Horse shows have to be canceled, and training centers have to be closed in order to prevent further spread of the disease once the virus is identified on the premises. There is no effective vaccine against the disease, and it is also proposed that frequent vaccinations with the currently available vaccines may even exacerbate this particular form of disease. With this proposed research we will study the pathological events occurring at the spinal cord of horses in an in vitro system. The outcome of this study will significantly influence therapies and vaccination schedules or vaccine development.
(back to top)
Studying The Use Of A Drug To Prevent Equine Herpes Infection
Lara Maxwell from Oklahoma State University
Our research team has recently found that the use of an antiviral drug (valacyclovir) early in the course of equine herpes virus (EHV-1) infection can protect horses from disease. Drug treatment decreased the amount of infectious virus that horses shed from their nose, decreased the horses’ fevers and other signs of illness, and reduced the neurological disease that can result from EHV-1 infection. This protective effect of drug treatment was seen both when valacyclovir was given before EHV-1 infection and when treatment was given just after horses started to develop fevers from infection. However, outbreaks of neurological EHV-1 may not be recognized until many horses have been infected with the virus for a longer period of time. When viral disease has had time to become established in a horse, drug therapy may not be as effective as it was when given early after infection. Therefore, stronger antiviral drugs may be necessary to avert neurological disease once the infection has become established. Valacyclovir might also be effective later in the course of infection, given its ability to control infection when given soon after horses spike a fever. It is not known at this time whether any antiviral drug can help horses with EHV-1 infection once the virus moves into the blood. Until the veterinarians and authorities dealing with an EHV-1 outbreak know which drugs will be effective at different stages of EHV-1 disease, these drugs cannot be used in the best way possible, so horses may receive no treatment or an ineffective treatment.
We are trying to determine whether delayed therapy with antiviral drugs can decrease the amount of virus in the blood and the neurological disease that develops from EHV-1. In addition, immunological tests are performed to try to identify the horses that will be most susceptible to neurological disease, so that horses with these characteristics could be identified during an outbreak and preferentially treated with antiviral drugs.
(back to top)
Completing The Genetics Of Equine Herpes And Increasing Our Understanding Of How Equine Herpes Emerges In Nature
Udeni Balasuriya from Gluck Equine Research Center – University of Kentucky
EHV-1 is one of the most clinically and economically important equine viral pathogens and a significant threat to the $102 billion US equine industry. The increase in incidence of EHM in recent years has given rise to considerable concern among horse industries and governmental agencies responsible for equine health throughout the world. Accordingly, it is imperative to identify all viral genetic determinants that are associated with the neurovirulence phenotype. As a first step towards achieving this long term goal, we propose sequencing multiple genes (as well as a selected number of full-length genomes) of a unique panel of archived EHV-1 field isolates of known neurovirulence phenotype. In summary, the primary goals of this research are to complete characterization of the genetic basis for EHV-1 neurovirulence in horses and increase our understanding of how these neuropathogenic strains emerge in nature.
These findings will yield important benefits for the equine industry in terms of improved diagnostics and more accurate predictions of the clinical consequences associated with detection of a particular viral genotype. Furthermore, sequence analysis of immunologically important viral surface proteins from an extensive array of EHV-1 isolates is important for the development of more effective vaccines, while better characterization of the viral DNA polymerase may help in the design of antiviral agents. (back to top)
Developing Better Tools To Study Immunity To Equine Herpes
Paul Lunn from Colorado State University
Equine Herpesvirus-1 infection causes enormous suffering in horses and extensive economic losses through frequent outbreaks of a range of diseases including epidemic respiratory disease, abortion, neonatal foal death, myeloencephalopathy, and chorioretinopathy. In the Thoroughbred industry, EHV-1 infection has at least three effects. Firstly, the clinical signs of respiratory disease in racing Thoroughbreds are more severe in younger horses, leading to frustrating delays in their athletic training program for lucrative “classic” races. Secondly, abortion occurs during the second half of pregnancy, causing enormous economic loss and with obvious equine welfare implications. Thirdly, outbreaks of neurological disease and abortion not only have welfare implications for the individual animals but can also lead to movement restrictions, thereby disrupting breeding or training schedules and causing management difficulties at racetracks and pre-training centers. During the past 3 years there has been a considerable increase in the reporting of outbreaks of neurological disease in North America and in Europe. The impact of EHV-1 infection, both real and as perceived by the industry and public may never have been higher.
It is imperative to develop better tools to study immune responses to EHV-1 if we are able to develop and test effective vaccines and understand how best to control disease due to EHV-1. The best available technology for this purpose is tetramers, and we are now ideally placed to synthesize these powerful tools. We are committed to sharing these reagents widely with other EHV-1 Researchers, which will facilitate EHV-1 research throughout the equine scientific community.
(back to top)
Studying A Drug To Protect Horses And To Limit The Contagious Period For Equine Herpes
Lara Maxwell from Oklahoma State University
The EHV-1 virus seems to cause more disease in adult horses now than it did in the past. This may be due to a change in the virus that has resulted in severe neurological disease in even well-vaccinated horses. The resulting outbreaks of EHV-1 have had a considerable impact on the U.S. racing industry, causing quarantines of racetracks at numerous U.S. tracks. The quarantines have been particularly problematic to horse that travel, due to subsequent restrictions on horse transport. The proposed study was designed to test whether drug therapy would be effective in a barn where a horse develops a fever due to EHV-1 infection and its stall mates are in the process of being exposed to the virus. These findings have the potential to be enormously important to the racing industry, because effective drugs would protect horses from crippling disease and limit the contagious period of virus infection.
(back to top)
The Development Of A Model To Study Equine Herpes Infection Which Will Significantly Influence Therapies And Vaccination Schedules Or Vaccine Development
Lutz Goehring from Colorado State University
The development of a model to study Equine Herpes infection which will significantly influence therapies and vaccination schedules or vaccine development.The neurological form of an Equine Herpesvirus-1 infection is an enormous and potentially growing threat to the equine industry- it is not only because horses with irreversible disease have to be euthanized, it is because of the infectious nature of EHV-12 that Thoroughbred races and Horse shows have to be canceled, and training centers have to be closed in order to prevent further spread of the disease once the virus is identified on the premises. There is no effective vaccine against the disease, and it is also proposed that frequent vaccinations with the currently available vaccines may even exacerbate this particular form of disease. With this proposed research we will study the pathological events occurring at the spinal cord of horses in an in vitro system. The outcome of this study will significantly influence therapies and vaccination schedules or vaccine development.
(back to top)
Studying The Use Of A Drug To Prevent Equine Herpes Infection
Lara Maxwell from Oklahoma State University
Our research team has recently found that the use of an antiviral drug (valacyclovir) early in the course of equine herpes virus (EHV-1) infection can protect horses from disease. Drug treatment decreased the amount of infectious virus that horses shed from their nose, decreased the horses’ fevers and other signs of illness, and reduced the neurological disease that can result from EHV-1 infection. This protective effect of drug treatment was seen both when valacyclovir was given before EHV-1 infection and when treatment was given just after horses started to develop fevers from infection. However, outbreaks of neurological EHV-1 may not be recognized until many horses have been infected with the virus for a longer period of time. When viral disease has had time to become established in a horse, drug therapy may not be as effective as it was when given early after infection. Therefore, stronger antiviral drugs may be necessary to avert neurological disease once the infection has become established. Valacyclovir might also be effective later in the course of infection, given its ability to control infection when given soon after horses spike a fever. It is not known at this time whether any antiviral drug can help horses with EHV-1 infection once the virus moves into the blood. Until the veterinarians and authorities dealing with an EHV-1 outbreak know which drugs will be effective at different stages of EHV-1 disease, these drugs cannot be used in the best way possible, so horses may receive no treatment or an ineffective treatment.
We are trying to determine whether delayed therapy with antiviral drugs can decrease the amount of virus in the blood and the neurological disease that develops from EHV-1. In addition, immunological tests are performed to try to identify the horses that will be most susceptible to neurological disease, so that horses with these characteristics could be identified during an outbreak and preferentially treated with antiviral drugs.
(back to top)
Completing The Genetics Of Equine Herpes And Increasing Our Understanding Of How Equine Herpes Emerges In Nature
Udeni Balasuriya from Gluck Equine Research Center – University of Kentucky
EHV-1 is one of the most clinically and economically important equine viral pathogens and a significant threat to the $102 billion US equine industry. The increase in incidence of EHM in recent years has given rise to considerable concern among horse industries and governmental agencies responsible for equine health throughout the world. Accordingly, it is imperative to identify all viral genetic determinants that are associated with the neurovirulence phenotype. As a first step towards achieving this long term goal, we propose sequencing multiple genes (as well as a selected number of full-length genomes) of a unique panel of archived EHV-1 field isolates of known neurovirulence phenotype. In summary, the primary goals of this research are to complete characterization of the genetic basis for EHV-1 neurovirulence in horses and increase our understanding of how these neuropathogenic strains emerge in nature.
These findings will yield important benefits for the equine industry in terms of improved diagnostics and more accurate predictions of the clinical consequences associated with detection of a particular viral genotype. Furthermore, sequence analysis of immunologically important viral surface proteins from an extensive array of EHV-1 isolates is important for the development of more effective vaccines, while better characterization of the viral DNA polymerase may help in the design of antiviral agents. (back to top)
