WSU study aims to identify drugs dangerous to cats with MDR1 mutation

Close up image of grey tabby cat with white on it's chin, neck and front paws.

Washington State University is recruiting pet owners to participate in a study if their cat has experienced an adverse reaction to certain drugs.

Up to 4% of all cats, approximately 4 million in the U.S. alone, have either one or two mutated copies of the MDR1 gene, which can make common medications, including those used for parasite control, potentially lethal, even when used at recommended dosages. Cats with two mutated copies – homozygous – are at increased risk of adverse reactions.

The study, led by Dr. Katrina Mealey, who initially discovered the MDR1 mutation and invented the first test to detect the condition, is specifically targeting cats that may have experienced a neurological adverse reaction to NexGard COMBO (eprinomectin), Centragard (eprinomectin), Profender (emodepside), Revolution (selamectin) or Cisapride (compounded formulation).

“Adverse drug event data we have collected in conjunction with results we have obtained from cell culture studies support our hypothesis that label doses of certain drugs may cause serious neurological toxicity in cats with the MDR1 mutation,” Mealey said. “Our goal is to identify cats that may have experienced a neurological adverse reaction to these products and determine their MDR1 genotype to see if there is an association between susceptibility to neurological adverse events and the feline MDR1 mutation.”

The MDR1 gene codes for P-glycoprotein, a component of the blood-brain-barrier. P-glycoprotein normally helps protect the brain from potentially toxic substances by pumping them out of the brain and back into the bloodstream. Cats with the MDR1 mutation have a deficient blood-brain-barrier, so drugs that are safe for most cats because they never reach the brain can cause serious neurological adverse effects.

DNA samples will be obtained from cats that qualify for the study to determine their MDR1 genotype. Cat owners and veterinarians from throughout the country are asked to participate. WSU will pay for shipment of DNA samples for cases that qualify for the study. While WSU offers both canine and feline MDR1 genotyping for $70, cats that qualify for the study will undergo MDR1 genotyping at no cost to owners.

Mealey said the current study was launched in response to a recent influx of feline MDR1 genotyping submissions because of drug-induced neurologic adverse drug events, including some deaths.

“If we can determine a drug is causing adverse reactions in cats with the MDR1 mutation,” Mealey said, “we can recommend that an appropriate warning be included on applicable product labels.”

Mealey and her team have already identified some medications, including products containing eprinomectin and ivermectin, that can put cats with the MDR1 mutation at increased risk of adverse reactions, but they suspect additional drugs might be causing adverse reactions in cats with the MDR1 mutation. Cats with the mutation may experience lethargy, ataxia, muscle tremors, disorientation, blindness, muscle weakness, and death when treated with the drugs.

The MDR1 mutation is more common in non-purebred cats, with the exception of Maine coons, which appear to have a higher representation than any other pure breed. Mealey recommends all cats be tested for the mutation to avoid preventable adverse reactions to medications.