WSU News

Team pursues personalized medicine for animals

Mealey and Court
 
Katrina Mealey, a pharmacologist and internal medicine specialist, and Michael Court, a board certified veterinary anesthesiologist. Photo by Henry Moore, Jr.  BCU, College of Veterinary Medicine
 
PULLMAN, Wash. – Washington State University’s College of Veterinary Medicine has established the profession’s first dedicated research effort pursuing individualized medicine in animals.
 
Individualized medicine, also called personalized medicine, has exploded in human healthcare thanks to a growing understanding of health and disease at the molecular/genetic level. Discoveries are coming quickly and move in record time from the lab bench to the bedside where they are recognized as new, justifiable clinical practices. 
 
On the human side, the leading institutions are Mayo Clinic, Johns Hopkins University, and Duke University to name a few.
 
“Establishing a research emphasis for advancing individualized animal medicine is long overdue in veterinary medicine,” said Bryan Slinker, dean of the veterinary college and the person who green-lighted the research priority. “Human medicine is significantly ahead of veterinary medicine in this area and we want WSU to be the first and the best center for advancing individualized medicine for the entire veterinary profession.”
 
There are only a handful of veterinary researchers in the U.S. who are recognized experts in pharmacogenomics and individualized veterinary medicine. 
 
Pharmacogenomics is research directed at identifying genetic variants and related mechanisms at the molecular level that determine how an individual animal reacts to a given drug. That determination is important not only to avoid adverse effects but to optimize benefits an individual may receive that were otherwise unknown.
 
One of WSU’s experts, Professor Katrina Mealey, a pharmacologist and internal medicine specialist who heads WSU’s Veterinary Clinical Pharmacology Laboratory, recognized the need to bring together a core group of pharmacology experts at the same institution. She recruited Professor Michael Court, a board certified veterinary anesthesiologist, who has contributed significantly to the field of pharmacogenomics and individualized veterinary medicine. They are recruiting a third faculty member.
 
According to Mealey, by creating a research team focused on individualized veterinary medicine, advances can be made more quickly than if these researchers were working independently at different institutions.
   
Most people are aware of individualized medicine but have never really thought about it. The average person knows someone who can’t take a given drug because they are allergic or for some other reason.
 
Conservative estimates of adverse drug reactions in human medicine range from one in 10 hospitalized patients and greater. Most studies estimate that up to 50 percent of these costly medical events could be preventable. 
 
One example from human medicine is two people who enter a hospital for the exact same surgery by the same surgeon and the same anesthesiologist. Both weigh the same, are the same sex and have identical lifestyles. Both undergo general anesthesia, receive the exact same drug dosages and have identical procedures performed.
 
In the recovery room, one patient recovers from anesthesia in the expected time of 30 minutes to an hour. The other patient doesn’t arouse, has to be placed on a ventilator and is sent to the intensive care unit for three or more days before stirring. What went wrong?
 
“Nothing went ‘wrong,’ per se,” said Court. “What likely happened is that traditional ‘one-size-fits-all’ medicine ran headlong into individualized medicine.”
 
“The one-size-fits-all approach in medicine, human or animal, served us well in the absence of any other information,” explained Mealey, discoverer of the MDR1 gene mutation that renders some dogs susceptible to the toxic effects of certain drugs.  Those drugs include ivermectin used to control parasites, the anti-diarrheal loperamide (brand name Imodium) and some anti-cancer drugs. 
 
Mealey’s discovery was one of veterinary medicine’s first molecular level tests attesting to the value of individualized medicine.
“Today, however, we have some tools to provide the information needed to separate patients into different populations based upon their genetic and molecular profile,” she said. “That profile may separate them based upon susceptibility to disease or, in our area of interest, how they might react differently to the same drug.”
 
“The information generated from each individual may not always be used to just prevent a negative event from happening to a susceptible population,” continued Court. “In the case of cancers and chemotherapy, an individual’s profile may help us select the most effective drugs, minimize side effects and avoid drugs that will not be successful. 
 
“Currently, our treatment regimens for most illnesses are based upon the best chance for the best outcome,” he said. “It’s a best guess, if you will, because we have no information to do otherwise. At the same time, we know a given regimen for a given disease that works well in some patients, even most, may not be at all effective in other patients.
 
“That is the core concept of individualized medicine and underlies the need for genetic and molecular information from each patient,” he said.
 
Court’s project involves a sensitivity of some sighthound breeds, such a greyhounds, to certain injectable anesthetic drugs. Like the human hypothetical case above, some greyhounds don’t regain full consciousness easily after general anesthesia. This has been known as a problem for many years by veterinarians, but the exact reason remains a mystery.  
 
Consequently, he is trying to determine if there are any genetic or molecular reasons for the unusual sensitivity that might give insights into problems that this breed (or related breeds) might have with other drugs.
 
Purebred dogs with a known problem (like the greyhound) provide an excellent opportunity to identify the important gene differences that affect an animal’s response to a particular drug. 
 
In the course of developing purebred dogs, people have selected individual animals for breeding that had one or two desirable characteristics. However, breeding for solitary traits also can bring along unexpected undesirable traits, and often at rates greater than would be encountered in random mating.
 
In the case of Mealey’s discovery, as herding breeds (the breeds most likely to have the MDR1 gene mutation) were developed, no one could have foreseen a mutation resulting in the drug intolerance. In fact, the drugs most affecting dogs with the MDR1 gene mutation had not even been discovered when the mutation was likely carried along in breeding.
 
“This is just the beginning,” said Mealey. “Our goals are to identify how drugs produce unanticipated adverse reactions in animals. By identifying the reason for the adverse drug reaction, we can either identify and exclude susceptible animals from treatment or use an alternative drug or dose for that animal.
 
“In the best case, we want to determine the optimal therapy for each patient, minimize adverse effects and maximize therapeutic effects,” she said. “This information will provide a basis for designing safer and more effective drugs for specific disease conditions as dictated by the individual.”