What's killing Lassie?
by Dena Marchant | © Washington State University
For years, veterinarians and dog owners have known that some collies can die when given Ivermectin, a drug commonly used against parasites in animals and humans. But no one knew why.
That is until Katrina Mealey, a researcher in the Washington State University’s College of Veterinary Medicine, suspected P-glycoprotein was involved. P-glycoprotein is thought to have developed to protect the body from environmental toxins.
To test her theory she needed blood samples from collies. Enter Dot Newkirk, a microbiologist with an office a few doors down from Mealey’s. Newkirk, a collie owner, enlisted the help of the Inland Empire Collie Club in Spokane.
“I expected eight or 10 dogs,” says Mealey.
“They got 42 collies,” says Newkirk, “which is just about every collie in the Spokane-Coeur d’Alene area.”
Adds Mealey, “We took blood samples until two in the morning.”
Having analyzed the blood samples from these dogs, Mealey thinks she may have found the answer to the puzzle. The answer, it turns out, has implications in the treatment of AIDS and cancer.
A gene known as the multi-drug resistance gene, mdr1, normally codes for the production of P-glycoprotein. P- glycoprotein is found in high concentrations in the intestines, the placenta, the brain, and the adrenal glands of dogs and other mammals, including humans.
Mealey found that in susceptible collies mdr1 contains a “deletion mutation.” Parts of the genetic code are missing. As a result, synthesis of P-glycoprotein is unsuccessful.
Ivermectin is a powerful neurotoxin. In normal collies, P-glycoprotein pumps this toxin from the brain. In collies with a deletion mutation in the mdr1 gene, P-glycoprotein is no longer available to protect the brain. After a single dose of Ivermectin, a dog with the mdr1 mutation begins to show signs of neurologic toxicity, which include unsteadiness, dilated pupils, and excessive salivation.
Mealey found that about one-third of collies have the genetic anomaly that stops production of P- glycoprotein.
Mealey is working on a simple test that collie owners and veterinarians could use to detect Ivermectin sensitivity. WSU has applied for a patent for the test.
Humans also have the mdr1 gene. As in dogs, the mdr1 gene synthesizes P-glycoprotein. Although P-glycoprotein protects the body from toxins, it also plays a role in preventing the absorption of HIV-1 protease inhibitors, drugs used to fight AIDS.
It may be possible to suppress the production of P-glycoprotein on a short-term basis in order to enhance the uptake of protease inhibitors in human AIDS patients, says Mealey. The same is true for other drugs such as those used to treat some cancers.
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