Metabolic Profiling Yields Insight Into OCD - Horse Racing News | Paulick Report
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Metabolic Profiling Yields Insight Into OCD

Researchers are using the complex science of metabolic profiling to determine why some young horses develop osteochondrosis dissecans (OCD) while others of similar breeding and management do not.

OCD is a common developmental orthopedic disease of young horses that causes lameness and affects the articular cartilage, growth plates, and cervical vertebrae (those in the neck). It may also be a factor in the formation of subchondral bone cysts. The disease occurs when the process whereby cartilage turns into bone is altered. In utero, the bones of a fetus begin as cartilage and then gradually mineralize into bone. This process is not complete at birth but continues throughout the first 14 months of a horse's development.

Dr. Sarah Ralston, VMD, PhD, an equine nutritionist at Rutgers University, and Dr. Istvan Pelczer, Ph.D., a pioneer in Nuclear Magnetic Resonance (NMR) Spectroscopy-based metabonomic analyses at Princeton University, have spent the past 10 years analyzing and graphing blood samples from Thoroughbreds and Standardbreds with and without OCD to see how their bodies' metabolic profiles differ. Armed with the spectroscopy data, the researchers have uncovered potential abnormalities in metabolic pathways that they believe can be manipulated to reduce the risk of developing OCD.

Technically, the science they're using is called metabonomics, a field that has been used in human medicine for decades to uncover risk factors for heart disease, autism, and renal disease. A closely related field, metabolomics, uses mass-spectrum chromatography to obtain similar results. Metabolomic analysis measures about 400 known compounds; NMR-based metabonomics reveals hundreds of identified compounds as well as previously unknown compounds, which are estimated to number in the thousands.

Based on their results, Ralston and Pelczer have applied for a patent to produce a supplement or a special feed they hope will normalize the metabolism of horses predisposed to OCD. Among the ingredients of the proposed supplement/feed are ascorbic acid, thiamine, omega-3 fatty acids, tryptophan, glucosamine hydrochloride, and chondroitin sulfate, plus optional ingredients vitamin E, calcium, phosphorus, copper, zinc, pantothenic acid, vitamin B12, hesperidin complex, and lipoic acid.

The metabolic profile shows two distinct clusterings. Green dots indicate horses with OCD; blue dots are non-OCD horses.
The metabolic profile shows two distinct clusterings. Green dots indicate horses with OCD; blue dots are non-OCD horses.

According to Ralston, a Fulbright scholar, both fields metabonomics and metabolomics are extremely complex and difficult to grasp, even for someone with advanced knowledge of science.

It took me over seven years working in this field to wrap my head around it. It is terribly complex,” she said, crediting Pelczer as her guru in this project.

Each data point on the graph represents one spectrum — one animal or one sample,” Ralston said. “Then we color-coded these spectra according to whether the animal had OCD or did not have OCD. We got clear and distinct clustering of all the OCDs in one distinct group, and the non-OCDs were in another group. Then we went back into the program and asked it, 'What are the peaks that are contributing the most to that cluster? What are the most important components of the profile that make them so distinctly different?'

“When we asked the program, 'What are the variables of importance?' it tells us it's this amino acid, or this breakdown byproduct of a vitamin, etc.”

Based on these results, the researchers hope to modify the defective pathways by designing a feed to address them. For example, if there are issues with the antioxidant pathways, they add antioxidants to the diet.

Ralston and Pelczer haven't determined whether the patented product should be a supplement or a total feed, although Ralston said it would be easier to control the overall ingredients in the horse's diet if it were produced as a commercial feed instead of a supplement to an owner-provided ration.

Peaks on the graph indicate variations in the metabolic pathways that define horses with OCD and non-OCD horses.
Peaks on the graph indicate variations in the metabolic pathways that define horses with OCD and non-OCD horses.

Because OCD has a strong genetic component, at least in Standardbreds, the supplement or feed is designed to be fed to pregnant mares at risk for producing foals that develop OCD. Then those resulting foals would be fed the supplement or feed until they reach 14 months of age, which studies have shown to be the range during which young horses develop OCD.

As in its diverse use in human medicine, success in the area of equine developmental orthopedic disease promises to lead to the use of metabonomics and metabolomics to determine risk factors for other equine conditions and diseases, such as laminitis.

While Ralston and Pelczer continue their work, they also are meeting with feed companies to negotiate the best partnership to produce the product.

“This is a work in progress,” Ralston said. “I don't think we have the complete picture yet, but we're working on it. It's so exciting, and it's a lot of fun to work with it because of the potential. Stay tuned!”

 

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