PrIMe graduate student identifies gene essential for effective pain treatment in dogs
Tramadol is one of the most widely prescribed drugs for treatment of mild to moderate pain in dogs. However, there is growing evidence that this drug may not work well in some patients because of genetic differences. Dr. Tania E. Perez-Jimenez (DVM, MS), a graduate student in Dr. Michael Court’s Pharmacogenomics laboratory, has identified a gene that is essential for “turning on” the pain relieving effects of tramadol in dogs. The gene called CYP2D15 produces an enzyme that converts tramadol into M1. Tramadol by itself lacks any pain relieving effects and must first be converted into M1 in the liver before it can alleviate pain. A related gene in humans (CYP2D6) produces a similar enzyme that is essential for forming M1 from tramadol in people. However, tramadol is ineffective for treating pain in 5 to 10% of people because they have a mutation in CYP2D6 and do not produce sufficient amounts of M1. Consequently, the next step in the project is to determine whether there are mutations in the canine CYP2D15 gene that could also explain why some dogs do not achieve adequate pain relief from tramadol. Dr. Perez’s discoveries were recently reported in the journal Drug Metabolism and Disposition (PMID: 27758804), and were funded by a Morris Animal Foundation Training Fellowship and the William R. Jones Endowment at WSU.
PrIMe research team develops assay for immunosuppressant drug to improve its safe use in dogs and cats
Mycophenolic acid (MPA) is the active metabolite of the immunosuppressant prodrug mycophenolate mofetil. In this study, we developed and validated a novel ultra-high performance liquid chromatography (UHPLC) method for the rapid quantification of MPA in plasma from dogs, cats and humans. The advantages of this method include: high sensitivity and reproducibility over a wide range of MPA plasma concentrations, small sample volume and easy sample preparation. By combining isocratic conditions with a UHPLC columncontaining solid core particles, we were able to elute MPA within 3.0 min. The very short chromatographic analysis time makes this method ideal to study the disposition of MPA in large batches of plasma samples and/or monitor plasma drug concentrations, as recommended for patients that require optimized immunosuppression.
PrIMe researcher receives grant to improve safety of pain medications for cats
Cats are the most common pet in the United States. Every year, thousands of cats unnecessarily suffer from pain and inflammation when they could have benefitted from treatment with non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam. This is because relative to most dogs and humans, cats are more likely to experience serious side effects from NSAIDs, limiting safe and effective inflammation and pain control in this species. Understanding the effects of NSAIDs on cellular metabolism in cats will help unveil the mechanism underlying their predisposition to serious side effects relative to other species and open the way to substantial advances in the treatment of inflammation and pain in these animals. In this study we will determine the effects of chronic meloxicam administration on cellular metabolite profiles in cat plasma and urine. We will apply an untargeted metabolomics approach that will allow us to identify currently unknown metabolite changes that could explain why cats are predisposed to adverse effects of the NSAID meloxicam.
AKC awards $150,000 to PrIMe laboratory for Sighthound genetic research
The American Kennel Club (AKC) has awarded $150,000 to Dr. Michael H. Court BVSc, PhD (principal investigator) and Dr. Stephanie Martinez, PhD. (postdoctoral fellow) to study adverse drug reactions in greyhounds and related sighthound dog breeds. The project entitled “Understanding the Genetics of Adverse Drug Reactions in Sighthounds” (AKC grant #02242) will determine the effect of several genetic mutations on drug metabolism enzyme function using cell-based model systems. These mutations were discovered in a targeted genetic screen of greyhound DNA and may explain why some greyhounds wake up slowly from a number of anesthetic drugs. Importantly, other sighthound dog breeds such as Scottish deerhounds and non-sighthound breeds such as border collies have this mutation. The ultimate goal is to develop a genetic test that could identify dogs at risk that will require different drugs or drug dosages.
AKC Canine Health Foundation
Genetic variant of drug transporter gene in cats predisposes to drug toxicity
A research team in the Program in Individualized Medicine identified a mutation in a gene encoding a drug transporter that is a key component of the blood brain barrier. The Animal Poison Control Center contacted Dr. Katrina Mealey when a cat that experienced neurological toxicity after being treated for ear mites. Using DNA from that cat, a 2 base pair deletion was identified in the ABCB1 gene (ABCB11930_1931del TC) . Mealey and her team then sequenced the gene in 100 other cats from the WSU College of Veterinary Medicine’s DNA Bank and found that approximately 4% of cats have the genetic defect. By knowing which cats have the genetic defect prior to treatment for ear mites (and other diseases), veterinarians can use alternative treatments and prevent adverse drug reactions in cats.
PrIMe graduate student awarded Morris Animal Foundation Fellowship
Dr. Tania E. Perez-Jimenez (DVM, MS) has been awarded a highly competitive 2-year Fellowship training grant from the Morris Animal Foundation in support of her PhD thesis project. Dr. Perez recently completed her training as a veterinary anesthesiologist in the WSU residency program under Drs. Tammy Grubb and Stephen Greene (PriMe faculty members); and is now receiving pharmacology research training in Dr. Michael Court’s Pharmacogenomics laboratory. The goal of her study is to improve the effectiveness of tramadol for pain relief in dogs through genetic testing and combination drug therapies. Although tramadol is widely used by veterinarians to treat mild to moderate pain in dogs, there is evidence that this drug may not work well in many patients because of genetic differences and administration of other interacting drugs. Her study will identify genes (and ultimately a gene test) that could be used to determine which dogs would respond best to tramadol. She will also identify which other drugs could interfere with the analgesic effect of tramadol (and should be avoided), and also which other drugs might boost the pain relief from tramadol (and could be given as a combination therapy).
Morris Animal Foundation
Launch of the WSU Program in Individualized Medicine
Carlee, a 7-year-old yellow lab, is a mutant. Like many of her human redheaded counterparts, Carlee has a mutation in the MC1-R gene, or melanocortin 1 receptor. The gene is responsible for producing melanin, a pigment that determines hair, or in this case, coat color. Because humans with red hair often have a lower threshold for thermal pain, researchers at the WSU College of Veterinary Medicine wondered if they would find similar results in ...