Gene-based laminitis research opens door to early diagnosis

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Scientists in the United States pinpoint biomarkers that could help identify the debilitating condition earlier.
Image by secarter

Scientists have made big strides in identifying the genetic pathways behind laminitis, pinpointing biomarkers that could help identify the debilitating condition earlier.

Laminitis affects horses of many backgrounds, ages and disciplines.

A horse’s hoof functions under demanding conditions, with the need to support a heavy, fast animal.

Laminitis occurs when inflammation and damage of the tissue takes place between the hoof and coffin bone. It causes lameness, diminished quality of life and often results in euthanasia.

Now, researchers at the University of Florida and University of Pennsylvania have delved into laminitis at a genetic level, focusing on the hoof tissue.

“Laminitis is a tough problem for the horse and its owner,” said Samantha Brooks, associate professor of equine physiology at the University of Florida.

“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.”

Dr Hannah Galantino-Homer
Dr Hannah Galantino-Homer

Laminitis studies have previously been hindered by the scarcity of genetic information specific to hoof tissues.

The researchers 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,” Brooks said. “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.

Hannah Galantino-Homer, senior investigator in laminitis research at the New Bolton Center, said the findings of the research had significantly enhanced understanding of supporting limb laminitis and its disease processes.

“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,” she said.

The research resulted in several key findings.

The first related to keratin, an important structural protein that helps maintain the structural integrity of materials such as 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 tyre; it may still be running but it loses appropriate function and slows down.

Another type of cell machinery often studied in laminitis is 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 targeting 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,” Brooks said. “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.

Galantino-Homer said: “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.”

Brooks described the findings as a big step in improving our understanding of laminitis. “Something that could be completely untreatable 10 years ago; in another 10 years we may be able to intervene and make a significant difference in the disease early on.”

 

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