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AVMA 2017: How Pets Can Advance New Drug Development for Humans
Translational research studies in pets can serve as a useful bridge between traditional animal models and human clinical trials.
According to Carol Robertson-Plouch, DVM, from Translational and Comparative Medical Research, LRL Strategic R&D Innovations at Eli Research Laboratories, who discussed the One Medicine approach to drug development in a presentation at the American Veterinary Medical Association Convention 2017 in Indianapolis, Indiana, pets could play a crucial role in improving medicines of the future.
The cost of drug development has risen dramatically in recent decades, as has the cost of conducting a clinical trial in humans. Because most failures in phase 2 clinical trials are associated with a drug’s efficacy, this suggests that drug research needs better predictors of efficacy as well as safety, she said. “If we can be more predictive, we can also reduce some of these costs,” she said.
Although the translational animal models that are typically used for efficacy studies are useful, Dr. Robertson-Plouch stressed that they are insufficient, especially because the models represent diseases that are induced under controlled environmental conditions. As a consequence, the predictive validity of many animal models is limited, she added. For example, only 11% of oncology drugs with encouraging data in mouse models have led to approval of drugs for humans.
In contrast, naturally occurring disease models in companion animals may be more predictive of similar or identical diseases in humans. In addition to occurring spontaneously, such diseases occur in pets that are living in the same environments as the people who develop the disease. The active disease targets are often the same, explained Dr. Robertson-Plouch, and the genetic causes may also be homologous.
In translational and comparative medical research in pets, several factors should be considered when deciding which drugs to take forward through the research and development process, said Robertson-Plouch. In particular, the drug should be for a relevant spontaneous disease in animals that parallels one in humans, and there should be a connective hypothesis between the 2 diseases. In addition, taking the drug forward should be cost-effective and feasible, she added.
Dr. Robertson-Plouch highlighted various conditions that are similar in animals and humans, including heart failure, obesity, and osteosarcoma. She also noted that canine degenerative myelopathy is similar to amyotrophic lateral sclerosis (ALS) in humans. “The [superoxide dismutase 1] mutation that is causal for some ALS patients is also associated with some cases of canine degenerative myelopathy.”
She discussed collaborative translational research efforts between veterinary medical and human medical institutions, adding that “advocacy groups are also taking notice and taking actions.”
These collaborations include the 2007 One Health Initiative between the American Medical Association and the AVMA—a policy that advocates for closer ties between human and veterinary medicine. The Morris Animal Foundation’s Golden Retriever Lifetime Study was also launched to produce data for translational comparative medical initiatives. More recently, the Paws for a Cure Summit was hosted by the Canines-N-Kids Foundation to help facilitate collaborative efforts aimed to improve the approach to pediatric and canine cancers.
Evidence is thus mounting, concluded Dr. Robertson-Plouch, that increasing use of spontaneously occurring animal disease models in the human health research and development archetype increase the probability of advancing successful molecules.
Dr. Parry graduated from the University of Liverpool, England, in 1997, and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC, where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.