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“Translational medicine” (or “translational research”) is the discipline concerned with translating knowledge from basic scientific research into practical tools for patient care. Basic research is driven by a desire to increase our fundamental understanding of a scientific area and provides the foundation and inspiration for clinical investigations. The goal of translational research is to bridge the gap between basic and clinical scientists in order to accelerate the development of novel resources or methods for the diagnosis, treatment, or prevention of disease. The phrase “bench to bedside” is used synonymously with translational medicine and makes reference to scientists working at bench tops in a laboratory and clinicians treating patients at the bedside.
To understand the link between basic and clinical research, consider the recent decoding of the complete genetic make-up of a boxer dog1. This work, an example of basic research, provided a detailed genetic map with information about the location, number, and structure of dog genes. While not a practical tool in the clinical setting, scientists are using this information to identify genes causing diseases. Recently, the genes responsible for degenerative myelopathy in multiple breeds2, cardiomyopathy in boxers3, and polyneuropathy in greyhounds4 were determined using tools created from this information. The identification of disease-causing genes enables the development of genetic tests that can be used by breeders to prevent affected puppies and by veterinarians to aid in diagnosis.
Most translational research is concerned with improving healthcare for people (e.g., to develop more effective drugs, less invasive diagnostic procedures, etc.). Human clinical trials, though, are tightly regulated by the Food and Drug Administration and are given the green light only upon successful completion of safety and efficacy trials in research animals. Dogs are often the subjects of preclinical trials because they naturally suffer from many of the same diseases as humans, and they are closer in body weight to humans than are laboratory rodents. As a result, dogs are among the first patients to benefit from translational research.
Members of the University of Florida Powell Gene Therapy Center are conducting preclinical studies in dogs for the treatment of hemophilia in humans. Hemophilia is a bleeding disorder that affects approximately 20,000 Americans, as well as pure bred and mixed-breed dogs. Hemophiliacs are unable to make the components of blood that act to stop bleeding. Current methods for the prevention and treatment of bleeding episodes involve frequent administration of blood and/or the missing components. Gene therapy is a novel technique wherein normal copies of genes are delivered to a patient to treat or prevent disease. Gene therapy trials for the treatment of hemophilia have been successful in animal models for as long as three years. Although currently unavailable to humans, client-owned dogs will be able to receive gene therapy by participating in the trials5.
Translational medicine also aims to facilitate the development of tools for customized treatment regimens. Variations in a patient’s DNA can alter their metabolism (break-down) of certain drugs and cause a poor response to standard therapies. For example, dogs that suffer from epilepsy must be administered drugs to prevent seizures. Phenobarbital is the most commonly prescribed anti-seizure medication, but many dogs do not respond well to this routine drug therapy and continue to have seizures. It is necessary to experiment with different drug combinations and/or dosages to manage the disease in these dogs. The ability to predict which drug(s) will be most effective in a patient would streamline the development of effective treatment regimens and minimize patient (and owner) anguish.
Forms of customized patient care are already practiced in veterinary clinics. In dogs, a genetic variation in a gene known as MDR1 causes sensitivity to certain drugs, including Ivermectin, a component of some monthly heartworm preventatives. Sensitive dogs are unable to pump the toxic drugs out of the brain and can suffer from intoxication, seizure, and death. Collies are the most commonly affected breed with about 70% of the population having the MDR1 variant6. Australian shepherds, Whippets, and Silken Windhounds are among the other breeds having high incidents of the variation (30-50%). Genetic testing for the MDR1 variant is available to help veterinarians and owners make informed medical choices. Knowledge of the breeds in which the variant has been found also helps veterinarians make generalized decisions about which medicines to prescribe for different breeds.
Historically, clinical applications are many years removed from the laboratory research on which they are based, in part because of an intrinsic disconnect between basic and clinical scientists. Translational medicine is an intermediate field of science that seeks to rapidly process information from basic research in order to facilitate the development of novel clinical applications. In short, translational medicine is a means to more rapidly achieve what is a common goal of scientists: to understand disease and thereby provide patients with superior and individualized medical care.
In this podcast we bring you an interview with Dr. Tim O’Brien, professor of veterinary anatomic pathology at the University of Minnesota College of Veterinary Medicine. Dr. O’Brien was funded by CHF to establish a laboratory-based system for understanding cancer stem cell development.
This podcast was made possible thanks to the generous support of the Kenneth A. Scott Charitable Trust, a KeyBank Trust.