Zweig Research Improving Equine Health:
Dr. Stephen Barr Battles the EPM Parasite

(Photo: Frank Dimero)

When a horse begins to wobble, becomes weak and uncoordinated, or has trouble standing or balancing, chances are it is a victim of equine protozoal myeloencephalitis (EPM). EPM is the most common neural disease in horses and accounts for more than one-third of all equine spinal cord disease in the United States.

"EPM is the most important infectious disease facing the equine industry today," says Stephen Barr, a New Zealand immunoparasitologist, protozoologist, and small-animal internist at Cornell who has been awarded a new Zweig grant to study the cause of the disease in detail. "It is fairly common and tends to affect certain farms."

Scientists first clinically recognized EPM in New York, Ohio, Illinois, and Pennsylvania during the 1970s. Since then, it has also been detected in Florida, Texas, Kentucky, and California and as far away as Central and South America. Usually afflicting young adult horses, the disease is especially prevalent in yearlings in training or in young racehorses. Veterinarians still don't know how long it takes for a horse to show clinical signs once it's been infected, although many assume the animals are infected early in life. Some veterinarians believe that clinical signs may be triggered by the stress of racing or even somehow by the administration of corticosteroids.

Without reliable diagnostic tests, veterinarians don't really know just how common the disease is, although at least 100 cases are diagnosed each year in just Florida, Texas, and Ohio. Once a horse has the disease, it is no longer useful for work or riding. "There are no drugs currently known that will kill the parasite, so once a horse has the disease, it's very difficult to treat," says Barr. "There are no vaccines for it either."

Scientists were able to link the disease to a protozoan about 20 years ago. But it wasn't until the early 1990s that the parasite, Sarcocystis neurona, was isolated from horse tissues. Previous Zweig funding helped support research to identify the parasite involved.

"Although no one really knows how or why horses become infected, we assume the infection is picked up by horses eating the parasite in the feces of opossums [spread on pasture], and that the parasite then makes its way from the horse's gut to the brain and spinal cord where it damages cells," says Barr.

His ultimate goal is to develop a drug or vaccine against the protozoan parasite.

"We are trying to identify important molecules, such as certain enzymes, in the parasite that have important functions and are essential for its survival and the progression of its life cycle," he explains. "If the function of a particular enzyme, for example, is removed or inhibited by the action of drugs or a vaccine, the parasite would die."

Because certain enzymes, or proteases, that are present in protozoan parasites are known to contribute to other diseases, such as AIDS in humans, protozoologists like Barr already know a great deal about the function and structure of many proteases. He is using this knowledge to help find similar proteases in the protozoa known to cause EPM.

He has already determined that the merozoites-the life stage of S. neurona that is responsible for the damage to the brain-contain a gene that expresses a type of protease (an aspartic protease) that previously had been shown to be important in allowing the HIV virus to enter cells. He also has identified major parts of two genes that he believes encode for two other proteases, one or both of which he suspects will be important for the survival of the protozoa in EPM.

"Once we're able to identify the entire gene, we not only will be able to determine how the protease will look and act, but also what its function is. If it is essential for survival, we will go ahead and make large amounts of it. Once made, we can use the protease to design drugs that inhibit the protease, and also use it as a basis to make a vaccine against it."

The parasite, however, has been particularly difficult to work with and to gather large amounts of genetic material from, says Barr. He is growing in his laboratory both the S. neurona parasite and S. falcatula, a very similar parasite which does not cause disease.

"We're feverishly trying to find genes in one that are not in the other. That way, we might be able to identify the gene that causes the disease," he says.

Barr is not only isolating and characterizing genes that express the enzymes he thinks will end up being important for EPM, he's also working with other genes he and his colleagues find. He feels that many of them could prove useful in drug testing and in the development of vaccines for other diseases in horses or other animals.