Digging into grass sickness

A rare horse disease shares similarities
with human neurodegenerative disorders

A horse suffering from grass sickness. BRUCE MCGORUM

Each year in the U.K., about 2 percent of horses die from grass sickness. No one knows what causes the disease, but it does occur almost exclusively in grass-fed animals, including ponies and donkeys. A similar disease is thought to afflict dogs, cats, rabbits, hares, llamas and possibly sheep.

Researchers recently reported their analysis of tissue samples taken from horses stricken with the disease in the journal Molecular & Cellular Proteomics. In their attempt to understand what happens at the molecular level of equine grass sickness, the researchers found misfolded and dysregulated proteins in the tissues that resembled those found in human neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.

Animals with grass sickness usually suffer gut paralysis. The animals roll, sweat, drool and have trouble swallowing. Animals acutely afflicted with the disease usually have to be euthanized.

The disease is known to attack the neurons, but the causative agent is not known. To get a look at what goes on at the molecular level, Thomas Wishart at The Roslin Institute in Scotland teamed up with Bruce McGorum at the University of Edinburgh’s veterinary school. The investigators applied proteomic techniques to samples taken from horses that came down with grass sickness.

Wishart says they do know which tissues are affected most consistently: “We considered that a proteomic analysis would provide a snapshot of the molecular processes in play within those samples at that point in time.”

He points out that the work described in the MCP paper “is the first application of modern proteomic tools and in-silico analytical techniques to equine neuronal tissues and to an inherent neurodegenerative disease of large animals that is not a model of human disease.”

The investigators found that the expression levels of 506 proteins were changed in the ganglia taken from horses felled by grass sickness. Moreover, some of the proteins were misfolded, aggregated or in the wrong places. The proteins included amyloid precursor protein, the microtubule-associated protein tau and several components of the ubiquitin proteasome system. These proteins have been implicated in human neurodegenerative disorders.

Finding this similarity between human and horse neurodegenerative diseases, says Wishart, suggests the aggregated or misregulated proteins are “more likely to be end-stage regulators or late consequences rather than initiators of the degenerative cascades.”

As equine grass sickness can be hard to diagnose in some horses, a next step for the investigators is to see if they can come up with a noninvasive diagnostic test.

Rajendrani Mukhopadhyay Rajendrani Mukhopadhyay is the chief science correspondent for the American Society for Biochemistry and Molecular Biology. Follow her on Twitter.