Dogs – best friends and clue to scientific breakthroughs

December 8th 2021
Meeraa Ramakrishnan and Renée Hartig

The importance of animal research has long been recognized in the field of advancing treatments for human diseases, yet some are still against it.

But if research in animals, specifically dogs, could lead to better treatment options and lives for the dogs themselves, would people still disagree?

Over the last decades, several scientists have worked on studying disease in dogs and translated their findings to advancements in human medicine, as there are over 350 diseases in common between the two species.

Treating and Preventing Cancer

One disease in particular that has afflicted both dogs and humans alike for several years is cancer. According to the American Veterinary Medical Association (AVMA), both humans and dogs suffer from cancer at approximately the same rate, and cancer therapies may be applied to treating cancer in both species.

In 2007, University of Illinois veterinary clinical medicine professor, Timothy Fan, began to test a new cancer therapy on pet dogs with naturally occurring lymphomas (lymphatic cancer) and osteosarcomas (bone cancer that starts within the bone). The testing of the anti-cancer drug PAC-1 in these dogs eventually led scientists to advance their understanding of cancer in the human body and prompted the researchers to enter the drug in phase I clinical trials, which have completed in 2020. This would not have been possible without dogs, according to Prof. Fan, who said that other cancer therapeutic studies rooted in pet dogs included immune-stimulating agents, which are often rejected by the immune system of other animals, such as the mouse.

Dogs being more similar to humans in terms of response to medications, as compared to rodents, make them an ideal subject for investigations into cancer and result in more frequent positive results. Fan said, “We’ve relied almost exclusively on murine [mouse] preclinical models, and we’ve been able to show that investigational agents are very good at fighting cancer in these models. But, only about 1 in 10 of the agents that show great activity in mice will show similar activity in humans.” Furthermore, studies testing the same drug in dogs have been extended to gliomas (a brain cancer similar to glioblastoma in humans) and found it to be safe. In fact, one of the dogs had a complete response, with a 100 percent reduction in the tumor mass 84 days after combination therapy, according to Fan.

Dr. Fan, a member of Anticancer Discovery: From Pets to People at the Carl. R. Woese Institute for Genomic Biology at the University of Illinois, has his own dog named Ember, yet is still an advocate for conducting research on dogs. He believes that by using dogs to help guide drug development for people, we could potentially present “new, innovative therapies that would otherwise never be available to dogs, to help them as well.”

Other researchers, such as Dr. David Vail from the University of Wisconsin-Madison, have studied new therapeutics with the primary purpose of improving canine life, while the focus on advancing human treatment took a backseat. Nevertheless, all results were linked to potential novel strategies for cancer management in humans, with Vail himself saying, “The implications of success would be quite large — for dogs and people”. 

The clinical trial, named ‘Vaccination Against Canine Cancer Study,’ will be the largest clinical trial conducted to date for canine cancer. The trial will study what is called a peptide vaccine that “targets proteins that occur in RNA rather than in the DNA” common to both dogs and humans, in an attempt to prevent cancer, instead of treating it. This line of clinical research may pave the way for a pan-cancer vaccine — if one already targeting multiple tumor types proves successful.

As part of a double-blind trial, veterinarians will screen the volunteer participants before administering to half of them a placebo, and to the other half a vaccine. The dogs will receive 4 doses and yearly boosters for as long as the study continues all the while monitoring the dogs in their normal environments. With over 800 participants currently enrolled in the trial, and 3 participating universities, the trial is predicted to run for 5 years and could introduce a new type of cancer therapy and understanding of the immune system if successful

Yet again, studying responses to treatments in dogs through comparative oncology will offer scientists the chance to further improve treatments for humans.

In benign cases, in both humans and dogs, when a tumor has been found, the best course of treatment is typically surgery. Though this process is typical and satisfactory in humans, canine cases may involve drastic steps, such as amputation. The situation worsens when considering metastatic cancer, which is why novel steps with dogs at the forefront of research are important, especially given that more than half of dogs, aged 10 years or older, are expected to develop cancer.

Gene Therapy

Besides direct oncological treatments and therapeutics, gene therapy is also making itself known in the field of dog research. In fact, studies involving gene therapy have reversed the direction of goals, applying treatments designed for humans to dogs suffering from similar diseases.

William P.D. Hendricks, Assistant Professor at Translational Genomics Research Institute, and other researchers from Ohio State University, have made a breakthrough discovery for dogs facing pulmonary adenocarcinoma (a naturally occurring lung cancer) . Results from their study suggest that the drug neratinab, a type of irreversible pan-HER tyrosine kinase inhibitor, often used in the treatment of breast cancer in humans, may have clinical relevance in the context of dogs that carry the HER2 mutation. HER2 is the human epidermal growth factor receptor 2 protein and is a growth-promoting protein situated on the outside of breast cancer cells.

Their study employed genomic mapping to find that nearly 40% of the tumors observed in dogs were a product of the HER2 mutation, providing essential information for possible applications of human drugs. Hendricks and colleagues say their next steps are to launch a clinical trial and study the effects of neratinab in dogs with HER2-mutant lung cancer.

Though this is proposed to take around 2 years, researchers are enthusiastic about applying their findings to people who have never smoked, yet are still patients of lung cancer, thus aligning the clinical needs of both humans and dogs.

Canine Pharmacogenetics

In line with identifying causes of cancer that arise due to environmental conditions and not controllable factors, such as smoking, researchers believe studying canine pharmacogenetics may help to better understanding the field of human health.

One study specifically looking at genetic variation was conducted at the University of Wisconsin-Madison. The study’s principal investigator, Lauren Trepanier, explained that genetic variation recorded in enzymes that help the liver neutralize toxic substances in the environment that a dog/human might come into contact with indicates that the ability to “deactivate environmental hazards” is dependent on the person. Thus, the risk of developing cancer is also dependent on the individual.

Applying the same concept, Trepanier believes this could be the case for dogs too, and is working with the research team to replicate four major types of glutathione-Stransferase (GST) enzymes and incubate them with possible carcinogens [cancer causing agents], such as heat-treated food, air pollution, and a type of herbicide linked to lymphoma and bladder cancer in dogs and humans. The researchers hope to discover whether a specific enzyme profile leaves dogs more susceptible to certain cancers, which could provide dog owners with information on which environments may not be the healthiest for their loving pet.

Retinal Dystrophy and Blindness

Outside the field of oncology, genetic alterations have been shown to influence other aspects of the body, such as sensory processing. The sense of vision, for instance, is affected by RPE65 gene mutations, which can be inherited, and result in blindness caused by retinal dystrophy. Although blindness is more common in older adult populations (in both dogs and humans), this dystrophy, or wasting away, of normal retina function can occur as early as from birth.

Animal studies can provide proof-of-principle for therapeutic approaches, and studies on dogs with inherited retinal dystrophies can help refine gene therapy treatments of blindness. “Dog eyes show many similarities to human eyes, for example, in size and morphology and also in density” of light-sensitive receptors. Genetic mutations often “occur in the homologous gene in both dog and man and the resulting phenotype in both species is comparable.” Thus, preclinical research on blindness in dogs presents an opportunity for dog owners facing difficult circumstances in the event their dog is affected.

Dog studies also afford additional avenues for dog owners to explore state-of-the-art treatment options, while also helping support preclinical translations to treatment for congenital blindness. Gene therapies approved for humans after safety and efficacy demonstration in dogs is a prime example of the interdependent relationship between man and dog.

Considering data from humans, ranging across Caucasian, Black and Hispanic ethnicities, there is a clear jump in the percentage of blindness for those over the age of 79 (see Fig. 1, left panel).  With the number of cases of blindness increasing over time (Fig. 2, right panel), between the turn of the 21st century and 10 years thereafter, statistical analyses, conducted by the National Eye Institute on the 2010 U.S. National Census data, project an increase in blindness cases across the population. These are alarming statistics, indicating a grave importance of blindness studies.

Figures from the National Eye Institute on the 2010 U.S. National Census data

Lyme Disease

While the prevalence of blindness in humans has increased substantially since the turn of the century, dogs have encountered increasing risk for Lyme Disease that goes hand-in-hand with human disease cases. A new study from the Companion Animal Parasite Council, a leading source on parasitic diseases that threaten the health of pets and people, was motivated by the rise in Lyme disease cases in the U.S. The study revealed that Lyme disease in dogs is increasing in endemic Northeast regions (where Lyme borreliosis is regularly found), and moving into U.S. regions not historically considered endemic.

Further, significant increases in canine Lyme prevalence were seen in some areas that have not yet reported significant human incidence. From these results, “it is reasonable to infer that canine prevalence is more sensitive to changes in Lyme risk and could serve as an early warning indicator for changes in human risk .” In this case, the safety of your pet against ticks reflects personal safety, and both species play a role in protecting one another.

Arthritis

The list of similarities between dog and human biological systems continues when considering other diseases and health conditions (e.g., arthritis). Osteoarthritis, or gradual wearing down of cartilage in the joints, can arise from knee injuries. Both humans and dogs are susceptible to knee injuries and osteoarthritis. Thus, in order to better understand the relationship between knee injuries and joint degeneration, researchers from Cornell University set forth with an interdisciplinary study on ACL injuries in dogs.

This study, a first of its kind, employed dogs with ACL-type injuries to study the role of lubricin as a potential biomarker for predicting future osteoarthritis. Cornell researchers reported that lubricin concentration increased in injured joints and may serve as an indicator of joint instability before any signs of arthritis are apparent by X-ray. Further research is warranted to better understand how lubricin may be tapped to prevent or mitigate arthritis symptoms.

Dog Research Benefits Humans and Dogs!

Overall, from the examples provided in this article and many others, it is clear that several scientific breakthroughs have been made possible by humans’ best friend. Dog lovers, dog owners, and dog researchers alike have demonstrated not only compassion for the species but also an understanding of their role in potentially improving human disease treatment. It is all too common that a beloved pet dog succumbs to illness and ageing. The lifespan of humans greatly outlives that of dogs, placing the burden of companion care on dog owners. A prominent tendency of pet owners is to go to all lengths to alleviate pain and suffering endured by their pets. To this effect, supporting scientific advancements to new horizons is mutually beneficial to both humans and dogs.   

This article is dedicated to one of the best pets anyone can ever ask for.

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