Equine veterinarians make steps toward solving the laminitis mystery - DVM
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Equine veterinarians make steps toward solving the laminitis mystery
An intensive area of study, laminitis still confounds researchers looking to advance our knowledge of disease origin, prevention and treatment. But some promising new research projects are looking to make great strides toward better understanding.


Laminitis research at the New Bolton Center

Hankenson is hoping to take a new approach to research. He has submitted a paper, a collaboration with Julie Engiles, VMD, DACVP, assistant professor of pathology at the New Bolton Center, looking at the changes associated in P3 following laminitis, using samples and case information from the Laminitis Discovery Database run by Galantino-Homer. "What we found is that there are some very pronounced changes that occur rapidly in the morphology of P3," says Hankenson. "We are interested in why those changes occur and what the role of those changes might be in the pathogenesis of laminitis."

This is a novel area in the field laminitis. Hopefully, Hankenson's studies will give us insight into laminitis treatment from looking at the bone perspective and insight into the pathogenesis of the disease, the relationship of the bone changes and that of the hoof. "My research has been focused on bone biology for many years—bone regeneration and healing and how bone changes over time," he says. "I'll be bringing that expertise into the project.

"Also related to bone biology, what I'm quite interested in, which is very specific to the Barbaro situation, is the condition of support limb laminitis (contralateral limb laminitis)," continues Hankenson. "With orthopedic injuries, if we can expedite the healing process it would be a way we could prevent laminitis. While bone heals well, we recognize that if we could accelerate bone regeneration, that might be an opportunity to get at-risk horses to bear weight on the injured limb faster, thereby preventing the support limb laminitis. So we'll also have an effort on how we can heal bone faster and also identify those bones that might be most at risk for injury. Can we identify horses that might be at risk for breakdown injuries, and can we return them to bearing weight in an expedited fashion?"

Hankenson has been studying mesenchymal stem cells for about 15 years. "That will be another area that we'll be focusing on—whether mesenchymal stem cells have any potential for treating laminitis, but also can mesenchymal stem cell therapeutics be better developed as an approach to treating bone regeneration," he says.

"What I find fascinating is that there are multiple factors that contribute to the development of laminitis," says Hankenson. "One of the questions that I think we need to explore is whether there is a point where there is a unifying mechanism that results in the breakdown of that laminar tissue, resulting in the clinical manifestations of founder. Or do we have multiple pathways that reach some common end result that is actually is something unique? We don't really have a good sense of this yet."

Perhaps the common systemic mechanisms have a common factor that leads to the cascade of laminitis. But does that agree with the contralateral limb problem? "I think that is something that still needs to be explored," Hankenson says. "In my opinion, the way to do that is exactly what we have been doing and will continue to focus on—building a large set of clinical data in naturally occurring horses with disease, and doing careful pathological analysis of the tissue as well as doing detailed molecular tissue analysis both locally and systemically. I think this is how we will get at the origin of the disease."

Galantino-Homer says the Laminitis Discovery Database can help. The database includes tissue and serum samples, gross images and histology slides from various sources, including the experimental models of University of Queensland Professor Chris Pollitt, BVSc, PhD; the oligofructose model of pasture laminitis; and the hyperinsulinemia model, which is a recent model for endocrinopathy-associated laminitis in horses with insulin resistance and hyperinsulinemia. It also includes samples from cases of naturally occurring laminitis from the hospital or from horses that are donated to the laboratory. Laminitis cases include supporting limb laminitis cases, sepsis and colitis cases, and horses with insulin resistance, pars pituitary intermedia dysfunction (Cushing's disease) and obesity.

"We're also developing an in vitro system, so that we can study some aspects of the disease without using live animals—in particular, the basal cells of the secondary epidermal lamellae, which are at 'ground zero' for laminitis pathogenesis," Galantino-Homer says. "There is only so much you can study using the naturally occurring laminitis cases, as these cases are typically euthanized late in the disease process, so it's hard to study the early stages of the disease. The disease 'snap shot' that we get from tissues collected at euthanasia or biopsy only provide information about a single stage of the disease, whereas the in vitro system can be used to determine what's happening at the cellular level in real time. That is difficult to do with the live animal."


Source: DVM360 MAGAZINE,
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