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Breakthrough Laminitis Research Opens Potential New Avenues For Treatment

Horse owners usually dread hearing the diagnosis of “Laminitis.” The disease plagues horses of many backgrounds, ages and disciplines. Using genetics, UF/IFAS and University of Pennsylvania School of Veterinary Medicine scientists have made a breakthrough in the disease thanks to funding from The Foundation for the Horse.

A horse's hoof has a tough job. It must support a heavy animal which can move faster than 40 mph. Laminitis occurs when inflammation and damage of the tissue takes place between the hoof and coffin bone. It causes lameness, a diminished quality of life and often results in euthanasia.

“Laminitis is a tough problem for the horse and its owner,” said Dr. Samantha Brooks, UF/IFAS associate professor of equine physiology. “We have very few tools in our arsenal to manage the disease itself. We treat symptoms, pain and mechanical instability but do not have anything to target the cause just yet.”

Laminitis studies have previously been hindered by the scarcity of genetic information specific to hoof tissues. Scientists tapped into the University of Pennsylvania's New Bolton Center Laminitis Discovery Database, an archive of data and sample sets from naturally occurring laminitis cases collected since 2008. Using that database, researchers examined 36 archived tissues of 20 Thoroughbred horses treated for laminitis.

There are three types of laminitis, and all impair the structure and function of the horse's foot. This research provided a snapshot of the active pathways and functions of the hoof, with a focus on supporting limb laminitis – the laminitis to which famous racehorse Barbaro succumbed.

“We understand the situations that trigger an episode of laminitis, but we do not have a good understanding of what is happening in the hoof,” said Brooks. “This study took a very comprehensive view of the processes early in the development of laminitis.”

Using gene expression analysis, researchers catalogued the changes in gene transcription across the 20 horses. Some had healthy feet, some were early in the disease process and others were more severe. Researchers identified trends in the disease process.

“By tapping into my lab's database and incorporating Dr. Brooks' unparalleled expertise in equine genetics and transcriptome analysis, we have identified new and promising pathways in cell stress and inflammatory response that significantly enhance our understanding of supporting limb laminitis and its disease processes,” said Hannah Galantino-Homer, VMD, PhD, DACT, senior investigator in Laminitis Research at Penn Vet's New Bolton Center.

The research resulted in three key findings.

The first related to keratin, an important structural protein that helps maintain the structural integrity of materials like hair, nails and horse hooves. This study was one of the first to examine the changes in the keratin family through the laminitis disease process. Some of the keratin-related genes and regulation of the cell's manufacturing process started to diminish as the disease began. This could be compared to when a car gets a flat tire; it may still be running but it loses appropriate function and slows down.

Another type of cell machinery often studied in laminitis are a class of enzymes called metalloproteinases; enzymes that help maintain the cytoskeleton. These enzymes must maintain a careful balance. Hooves must be able to grow and not break down under the weight of the horse, which requires a balance of remodeling and building tissues within the hoof. When the metalloproteinases become too active, the hoof begins to lose structural strength. One previous theory for treating this process was to stop these enzymes from becoming too active. But treatment targeted these enzymes might also stop hoof growth, which would likely lead to further issues.

When keratin degrades, inflammation in the hoof leads to laminitis. Scientists found a collection of genes responsible for triggering that inflammation which could pave the way for future medications to treat the inflammation. The genes led researchers to believe that some human inflammatory medications for autoimmune disorders may help horses with laminitis.

Changes in gene expression in diseased tissue are often reflected in changes in the proteins that can be detected in the blood as the disease progresses. For example, specific proteins, or biomarkers, that increase in the blood in humans following traumatic brain injury had increased expression in the samples from the horses with laminitis in this study. Medical doctors have used these compounds to understand the severity of these injuries in humans without using imaging or more invasive testing. Brooks hopes this could be used as a tool to monitor the progression of laminitis in the horse.

“We don't always recognize that a horse has severe laminitis until things have gotten quite bad,” said Brooks. “Early monitoring tools and ways to combat the disease were exciting findings, but we need further research before these new tools will be ready for use in the field.”

Brooks hopes that this research can lead to a blood test to detect these new laminitis-related biomarkers, and medications that are economical and effective for horses suffering from the disease.

“Ultimately, these new findings point us towards a more targeted approach for future exploration that we hope will help uncover novel solutions for preventing and treating this debilitating disease,” said Galantino-Homer.

“This is a big step in improving our understanding of laminitis,” said Brooks. “Something that could be completely untreatable ten years ago; in another ten years we may be able to intervene and make a significant difference in the disease early on.”

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International Veterinary Scholarship Program Launched For Equine Research

The University of Pennsylvania's School of Veterinary Medicine (Penn Vet) – together with the Royal Veterinary College (RVC) and MARS EQUESTRIAN™ – has launched a new, international scholarship program aimed at advancing the health and welfare of the horse while providing an unparalleled learning experience for one aspiring veterinary investigator.

Through its interdisciplinary, mentorship-based approach, the MARS EQUESTRIAN Veterinary Research Scholar program offers the unique opportunity to conduct research alongside internationally-renowned experts in equine health and veterinary welfare while pursuing two advanced credentials: the Graduate Certificate in Animal Welfare and Behavior at Penn Vet during year one, followed by the Master of Research (MRes) program at the RVC in year two.

Building upon Penn Vet's MARS EQUESTRIAN Early Career Investigator Program launched in November of 2020, this new format offers the candidate an exclusive opportunity to refine critical research skills and expand animal welfare knowledge while learning on location at both the RVC in London, England and Penn Vet's New Bolton Center in Kennett Square, Pennsylvania, United States.

Penn Vet's Dr. Kyla Ortved, assistant professor of large animal surgery at New Bolton Center, will serve as the primary mentor for the program's embedded research project. A clinical expert in equine orthopedic surgery and sports medicine, Ortved's research program seeks to better understand attributes of the equine joint in order to improve clinical outcomes associated with osteoarthritis following injury in horses.

“There are two fundamental components to a successful career in the veterinary medicine field: exceptional mentorship and the continuous pursuit of applicable knowledge,” said Ortved. “The multidisciplinary approach of the MARS EQUESTRIAN Veterinary Research Scholar program is set to provide both of these cardinal elements through an experiential learning environment that will ultimately culminate in delivering meaningful advancements that will have a very real, positive impact on the lives our equine partners.”

The selected candidate will also learn from leading experts in animal welfare including Penn Vet's Dr. Tom Parsons, professor of swine production medicine, director of Penn Vet's Swine Teaching & Research program and one of the founding members of Penn Vet's Animal Welfare and Behavior Certificate program. This certificate, coupled with the RVC's MRes program, will balance pragmatic understandings of multi-species health, behavior, and well-being with interdisciplinary problem-solving skills that can be directly deployed through the program's research projects.

“I am delighted that the RVC is able to support this new transatlantic initiative for veterinary graduates following a generous donation from MARS EQUESTRIAN,” said Professor Richard Bomphrey, Interim Vice Principal for Research at the Royal Veterinary College. “It strengthens the ties between the RVC, the University of Pennsylvania and MARS EQUESTRIAN while providing an outstanding training and research opportunity. We look forward to welcoming the successful scholar and helping them to make an impact in equine research.”

“MARS EQUESTRIAN is thrilled to support this truly unique and innovative international program unlike anything else offered in veterinary medicine training,” said Bridgett McIntosh, PhD, Director at MARS Equestrian. “Our goal is to continue to drive the field forward in creating a better world for horses by engaging and training the next generation of veterinarians.”

The MARS EQUESTRIAN Veterinary Research Scholar program is open to interested UK, US and international candidates holding a veterinary degree (DVM/VMD/BVSc or equivalent). The chosen candidate will receive an annual stipend and tuition as well as travel expenses. The program will commence in September 2021 in the United States before moving to the UK in October 2022 until its conclusion in September 2023.

The deadline to submit applications for consideration is June 30, 2021 or until an acceptable candidate is identified.

Reade more here.

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UPenn Researchers Develop Test To Detect Gene Doping In Racehorses

Researchers at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) have successfully developed a new test to systemically detect the local administration of illicit, gene doping therapies in equine athletes. The findings from the novel study, supported in part by the Pennsylvania Horse Breeders Association (PHBA) and the Pennsylvania State Horse Racing Commission, are a significant breakthrough in the collective fight to advance the welfare and integrity of sport for both horses and humans.

Unlike other small molecule pharmaceuticals, gene doping agents trigger cells to produce performance enhancing proteins. These proteins, which often are more elusive due to their virtually indistinguishable characteristics from naturally occurring proteins within the body, can make it more difficult to determine whether or not an animal or human has had gene therapy administered. Until now, that is.

Led by Mary Robinson, PhD, VMD, DACVCP, assistant professor of Veterinary Pharmacology and director of the Equine Pharmacology Laboratory at Penn Vet's New Bolton Center, the team of Penn Vet researchers have created and validated a quantitative real-time polymerase chain reaction test – commonly known as a PCR test – that is able to detect the presence of a gene doping agent in plasma and synovial fluid after its intra-articular administration in horses.

“For the first time, we have demonstrated that a PCR test performed on a blood sample can detect the local administration of a gene therapy into the joint of a horse,” said Robinson. “While this test is currently limited in that it can only detect a specific gene therapy, it provides proof of concept that a gene therapy administered into the joint can be detected in a blood sample in a manner that is quick, convenient, and consistent with our long-term goal of deploying pre-race testing someday in the future,” she added.

Not only were the Penn Vet researchers able to detect the presence of this product in equine joint fluid after gene therapy was administered intra-articularly, they were also able to detect it in blood for up to 28 days. This represents a significantly robust window of time that could be useful for pre-race as well as out of competition testing.

“The ability to detect the presence of these gene doping agents in blood after local administration to joints just magnifies the implications of this game-changing development,” said Joanne Haughan, one of the lead investigators on the study. “The science is closing in on those who seek to use these advancements for wrongful means; the more we learn with each study, the harder it will be for individuals who seek to cheat the system using gene doping strategies.”

This ongoing body of research in gene doping is being performed concurrently with Penn Vet's larger multi-tiered, multi-year project to expand upon New Bolton Center's equine BioBank. Established in 2017 using internal funds from the Raymond Firestone Trust Research Grant and expanded in 2018 with support from the PHBA, the growing database collects and analyzes multiple types of samples, looking for a myriad of potential biomarkers in equine athletes. With the goal of someday creating “biological passports,” researchers believe these biomarkers could also be key in detecting gene doping as well as predicting injuries before they happen.

“As breeders, protecting the health, safety, and well-being of our horses is a deeply profound and personal priority for our membership,” said Brian Sanfratello, Executive Secretary of the PHBA. “These scientific discoveries get us one step closer to our dream of someday keeping equine sport completely clean. We are proud to support Dr. Robinson and her team of experts as they continue to incrementally drive us closer and closer to making that dream a reality.”

With the completion of a third study on the horizon, Penn Vet's researchers seek to further expand and refine their testing methodology in order to create screening tests that would successfully identify multiple gene doping agents for even longer periods of time.

“We still have a lot of work to do to better understand the nature of bio-markers and how to fully harness their capabilities, but the science for detecting gene doping is getting there and much more quickly than any of us could have anticipated when we started this research,” added Robinson. “Ideas that once may have seemed unattainable – like a hand-held, stall-side testing device – are now coming into sight as real and tangible possibilities. We just need continued support to help get us there.”

Dr. Mary Robinson is an assistant professor of veterinary pharmacology and director of the Equine Pharmacology Laboratory at the University of Pennsylvania School of Veterinary Medicine.

Additional investigators on the study include Penn Vet's Faculty and Staff including Dr. Joanne Haughan, Dr. Zibin Jiang, Dr. Darko Stefanovski, Dr. Kyla Ortved, and fourth year Penn Vet student Ms. Kaitlyn Moss.

This study is currently supported in part by the Pennsylvania Horse Breeders Association and the Pennsylvania State Horse Racing Commission, in addition to grants from the University of Pennsylvania McCabe Fund (Ortved) and New Bolton Center's Raymond Firestone Trust Research Grant (Haughan and Robinson). Individuals or organizations who would like to support the program through a financial donation are encouraged to contact Margaret Leardi, Director of Development for New Bolton Center, at mleardi at vet. upenn.edu.

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Penn Vet Develops New Gene Doping Test

A new test developed by researchers at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) can detect the presence of gene doping in equines. Partly supported by the Pennsylvania Horse Breeders Association (PHBA) and the Pennsylvania State Horse Racing Commission, the findings, which systemically detect the local administration of illicit, gene doping therapies, are a significant breakthrough. Unlike other small molecule pharmaceuticals, gene doping agents trigger cells to produce performance-enhancing proteins, which often are virtually indistinguishable from naturally occurring proteins within the body, making it more difficult to determine whether or not an animal has had gene therapy.

The team of Penn Vet researchers has created and validated a quantitative real-time polymerase chain reaction (PCR) test–a term that has become common vernacular due to COVID-19 tests-which is able to detect the presence of a gene doping agent in plasma and synovial fluid after its intra-articular administration in horses.

“For the first time, we have demonstrated that a PCR test performed on a blood sample can detect the local administration of a gene therapy into the joint of a horse,” said Mary Robinson, PhD, VMD, DACVCP, assistant professor of Veterinary Pharmacology and director of the Equine Pharmacology Laboratory at Penn Vet's New Bolton Center. “While this test is currently limited in that it can only detect a specific gene therapy, it provides proof of concept that a gene therapy administered into the joint can be detected in a blood sample in a manner that is quick, convenient, and consistent with our long-term goal of deploying pre-race testing someday in the future.”

The researchers at Penn Vet were able to detect the gene doping agent in equine joint fluid after it was administered intra-articularly and in blood for up to 28 days, making it useful for both pre-race and out-of-competition testing.

More work is being done by Penn Vet with the goal of someday creating “biological passports” and screening tests that would successfully identify multiple gene doping agents for even longer periods of time. Researchers believe biomarkers could also be key in detecting gene doping as well as predicting injuries before they happen.

“We still have a lot of work to do to better understand the nature of biomarkers and how to fully harness their capabilities, but the science for detecting gene doping is getting there and much more quickly than any of us could have anticipated when we started this research,” said Robinson. “Ideas that once may have seemed unattainable–like a hand-held, stall-side testing device–are now coming into sight as real and tangible possibilities. We just need continued support to help get us there.”

The post Penn Vet Develops New Gene Doping Test appeared first on TDN | Thoroughbred Daily News | Horse Racing News, Results and Video | Thoroughbred Breeding and Auctions.

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