In one 2007 episode of the medical TV drama series House, when one of Dr. Gregory House's patients and the man's Old English sheepdog both die, a veterinarian ascribes the dog's death to heartbreak.
But nothing's ever that simple on the hit series. House quickly determines the dog had an MDR1 genetic mutation, making it victim to the man's antiparasitic medication ivermectin, which it had consumed.
That episode, "97 Seconds," tugged at heartstrings with its tale of a man and his dog, but the science was based on years of research and testing by Katrina Mealey, a Washington State University veterinarian and pharmacologist.
Mealey has developed new insight and genetic testing for dogs and cats that can potentially save them from harm and suffering.
Her interest was piqued when she was a Ph.D. student at Texas A&M College of Veterinary Medicine & Biomedical Sciences, where she began studying P-glycoprotein. This protein is vital in pumping foreign substances, such as medicine, out of the cell.
A gene called MDR1 helps code the protein, and a mutation on that gene will impact P-glycoprotein's ability to function properly. Mealey read about a case in the Netherlands where some mice were genetically modified to not express P-glycoprotein.
Mealey says the mice became infested with mites, so the researchers sprayed the room with ivermectin, an antiparasitic drug used commonly in animals. The results were unusual.
"All the mice that were knockouts for this protein — you know, genetically engineered not to express this protein — all of them died, but all the other mice were alive and happy," Mealey says.
The researchers discovered that the mice without P-glycoprotein showed a concentration of ivermectin in their brains 100 times higher than in the regular mice. This research clicked for Mealey, who remembered that the collie dog breed was sensitive to ivermectin. When she joined Washington State University, she determined that her focus would initially be on this protein and mutation.
P-glycoprotein primarily functions in mammals to pump toxins out of the intestines, liver and blood-brain barrier. Dysfunction of the protein can lead to neurological toxicity.
So clearly, the mutation was dangerous, and this led to the next question: Which dogs might have the mutation? Through collaboration with geneticists at the University of California, Davis, Mealey was able to identify the mutation's origins.
"We published an article that showed that, probably a dog in England in about the mid-1800s, a very good male dog, very good sheepherding dog, was probably the first to have the mutation," Mealey says.
The descendants of the Old English shepherd breed include Australian shepherds, border collies, English shepherds and Shetland shepherds.
"A dog in England in about the mid-1800s ... was probably the first to have the mutation."
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Mealey says ivermectin was initially approved for use in cattle, but veterinarians began using it to treat dogs for heartworms and intestinal worms. However, dosage matters, and Mealey stresses that commonly used medications like Heartgard, which has ivermectin in it, are administered at lower doses than those used to treat intestinal parasites.
But Mealey says that a single dose of ivermectin at a dosage to combat parasites such as roundworm could cause a dog with the MDR1 mutation to go into a coma.
Herding breeds, boxers and mixed-breed dogs can have the MDR1 mutation and suffer from adverse reactions to medicines such as imodium, milbemycin, and avermectin. (Avermectins are produced by microorganisms, whereas ivermectin is a chemically modified substance derived from a natural organism.)
Mealey has patented testing for veterinarians and pet owners to determine whether their dog has a mutation and if certain medications will impact their pet's health. She advises testing as puppies because some medication used during spaying and neutering young dogs can impact pets with the MDR1 mutation. And she notes that though about 25% of herding dogs do not have the MDR1 mutation, testing is still beneficial because otherwise they may be needlessly restricted from beneficial medications.
Over the years, gene testing for dogs began gaining traction, and Mealey's published research began circulating and catching the attention of animal poison centers, which started reaching out to Mealey and her team at WSU.
In one case, a whole litter of cats suffering from ear mites was treated with ivermectin and about half suffered severe neurologic toxicity, leading researchers to suspect a mutation in the MDR1 gene could also be found in cats. However, nothing developed further until multiple cat medications with the ingredient eprinomectin hit the shelves, and Mealey noticed more cases of neurological toxicity.
"Many cases were submitted to us, and it just looked obvious to us that there was a link between the MDR1 mutation and the serious neurologic toxicity in these products containing eprinomectin that were given to cats," Mealey says.
In a March news release, Mealey said she hoped that the findings will lead the U.S. Food and Drug Administration to evaluate and consider warning labels on products containing eprinomectin, noting that it may have adverse effects on cats with the genetic mutation. About 1% of the 60 million cats in the U.S. are predisposed to the mutation.
Ultimately, the research and testing created by Mealey and her team have led to improved standards of care for dogs and cats with the MDR1 mutation. Testing is now used to identify potential harm for pets before chemotherapy or anesthetic drugs are administered.
Mealey's research and advancements in pet medicine are just one component of the work done by the team in the Program in Individualized Medicine (PrIMe), which includes Tania Perez Jimenez and Michael Court, veterinarians specializing in anesthesia, and Nicolas Villarino, a veterinary clinical pharmacologist.
Other advancements developed by the team at PrIMe include Court's testing for the delayed postoperative hemorrhage gene (DEPOHGEN). This potentially fatal disorder leads to excessive bleeding hours or days after surgical procedures in pets.
Mealey says PrIMe faces funding challenges but the team is grateful for organizations such as EveryCat Health Foundation and Morris Animal Foundation, which help fund their important research.
When asked about pet owners' responses, Mealey says they've told her that the test helped save their animals' lives.
The earliest news of the MDR1 genetic testing for herding dogs was hailed by Dr. Marty Becker — dubbed "America's Veterinarian" — on Good Morning America as the best new pet product of 2010.
And the ongoing work by Mealey and her team at PrIMe is not just the work of fiction for a drama series but is actively changing the lives of people who care deeply about their cats and dogs. ♦
