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FROM BARK TO BEDSIDE Downloaded from Clinical trials in pets are ramping up, but will they benefit human health?

By David Grimm

rankie, a 15-year-old brown dachs- asleep at any moment. At least until veteri- removes blockers, which hund with a gray muzzle and tired nary internist J.D. Foster sticks a thermo- may allow her to better fight the cancer. If eyes, rests on a pillow and pink meter in her butt. the treatment works, it probably won’t ex- blanket on an exam table at the A black mass has engulfed Frankie’s tend Frankie’s life—but it could make her University of Pennsylvania School of bottom-right canine tooth—a last few months a lot more pleasant. It also Veterinary Medicine (Penn Vet). A that could eventually metastasize. If her just might lead to a new way to combat skin catheter draws blood from her neck owner had taken her to a traditional vet cancer in people, Foster says. He scratches into a gray machine the size of a clinic, the doctor would have likely recom- Frankie behind the ears as she closes her minifridge, which clicks and whirls mended removing part of her jaw, followed eyes on the pillow. “You’re a good girl,” as it returns clear fluid to her body through by a strong course of . But he coos. Fanother tube. The dog is strapped down by here at Penn Vet, Foster and his team are Frankie is the third of 13 canines in the a red leash, but the restraint hardly seems trying a new approach: cleaning Frankie’s study—a clinical trial that’s part of a growing

necessary; she looks like she could fall blood with an experimental polymer that push to develop new therapies for people by JOHN DONGES PHOTO:

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Published by AAAS Frankie the dachshund takes part in an experimental particularly poorly: Only 11% of oncology chief science officer with Ethos Veterinary melanoma trial at the University of Pennsylvania drugs that work in mice are ever approved Health, a new Woburn, Massachusetts– School of Veterinary Medicine. for people. based network of veterinary hospitals that “Drug development is not a sustainable plans to conduct clinical trials. “The mouse testing them in sick dogs and instead of model the way it is now,” LeBlanc says. “It’s has prove[n] itself time and time again to lab rats or mice. Pets are a better model of too much money and too much time.” be a bad investment. The dog is an alterna- human illnesses than rodents, advocates con- Enter pets. Unlike lab animals, which are tive to something we know doesn’t work.” tend: They live in the same environments, highly inbred and raised in environments sometimes eat the same food, and get many so sterile they typically only get cancer A COUPLE OF FLOORS DOWN from Frankie, a of the same diseases, particularly cancers, when researchers obliterate their immune brindle pit bull named Paisley is wagging that we do. So, the thinking goes, they could systems and inject them with tumors, dogs excitedly in a small exam room. Her owner, hold the key to developing new therapies for and cats are genetically diverse and live Chelsea Burns, holds her tight on a black humans at a fraction of the normal cost—and in the real, messy world. So it’s no sur- leash while a vet tech peppers her with ques- potentially yield a trove of new medicines for prise that they get diseases, from cancer to tions: How often does she eat? How are her pets themselves. arthritis to muscular dystrophy, that seem bowel movements? Burns hands over two “There’s an opportunity for everyone to mimic ours. A type of breast cancer in cats grocery store bags filled with poop. “She’s to benefit,” says Amy LeBlanc, who over- has been associated with the same protein— an overachiever,” she smiles sheepishly. sees pet clinical trials at the U.S. National HER2—as one of the most aggressive breast Paisley is here for a different clinical Institutes of Health (NIH) as the director cancers in women, and the bone cancer trial, one that aims to figure out whether of its Comparative Oncology Program in is nearly identical—both the gut microbiome—the ecosystem of Bethesda, Maryland. The number of such clinically and genetically—in dogs and intestinal bacteria linked to everything trials is booming, she notes, with hundreds people. That may be why a lot of the same from allergies to obesity—can give clues to conducted over the past decade. drugs help both us and our pets. The most which therapies best treat irritable bowel But others question whether these stud- common therapies for human non-Hodgkin disease. Today, Paisley will have a physi- ies will really have an impact cal exam and an to on human health. “It’s a very in- confirm she has the condition. on August 12, 2016 teresting idea, and it all sounds Tomorrow, she’ll get a colo- very nice,” says Larry Baker, noscopy and a of her an oncologist at the University intestines. If she qualifies for of Michigan, Ann Arbor, and the trial, she and 50 other dogs the former chairman of one of will spend 7 weeks on a special the largest human clinical trial diet—and possibly a course of organizations in the United antibiotics—with regular trips States. “But this field has yet to to Penn Vet for evaluation. prove itself.” It all sounds a lot like a hu- man clinical trial, and it is— PET CLINICAL TRIALS date back to replete with many of the same http://science.sciencemag.org/ the mid-1970s, when vets tested challenges. Burns has to sign vaccines in house- an eight-page consent form, for hold dogs. Later trials tackled one, and some pet clinical trial other cancers with proponents have suggested add- transplants and inhaled chemo- ing a “patient advocate” to such therapies—all with the hopes of studies to ensure that someone translating the approaches to other than the emotionally at- humans. But the studies were tached owner is looking out for Downloaded from few and far between, and there the or dog’s best interest— was no coordinated effort to two lines of red tape rat re- bring them into the mainstream. searchers don’t have to cross. That began to change about Paisley the pit bull gets an ultrasound as part of a clinical trial on irritable bowel What’s more, owners like a decade ago. More than half of disease at the University of Pennsylvania School of Veterinary Medicine. Burns consider their pets part U.S. households had pets by that of the family (“Paisley’s pretty point, and owners were spending billions lymphoma work in dogs, and those that much like my child,” she says), so there is of dollars a year on veterinary care alone. don’t work in dogs don’t work in people. a limit to the type of experiments that can There was also a growing crisis in the tradi- Researchers can also conduct more be done on them. No is going tional drug development pipeline. Typically, detailed studies on pets than they could in to euthanize someone’s dog at the end of researchers first test experimental therapies the past, thanks to advances in veterinary a trial to get a better sense of how a drug in laboratory rodents, then in larger animals medicine—from transplants to stem worked, for example, even though that such as monkeys, before moving to human cell treatments—and breakthroughs like could be incredibly informative. “You can trials. But the success rates have been abys- the sequencing of the dog and cat genomes. try just about anything in the rodent world,” S mal. It can take 16 years to bring a new drug to “We can ask much more scientifically rigor- says Dottie Brown, the director of the Veter-

D O NG E market, at a cost of up to $2 billion, and 10,000 ous questions that are more likely to inter- inary Clinical Investigations Center at Penn promising compounds may lead to only one sect with human health,” says Chand Vet. “But these are people’s pets.” O : J H N

T U.S. Food and Drug Administration (FDA)– Khanna, who founded NIH’s Comparative Dogs and cats have other disadvantages.

P HO approved treatment. Cancer therapies fare Oncology Program in 2003 and is now the The same things that make them good

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Published by AAAS NEWS | FEATURES models for human disease—more diverse in animal health studies. Things might be Academies of Sciences, Engineering, and environments and genetics—cause prob- easier if the field had notched some big Medicine, sparked new collaborations, and lems when scientists are trying to eliminate successes. But Baker, who made his repu- removed a major roadblock. The pharma- variables that could tell them why a drug tation treating children with osteosarcoma, ceutical industry had worried that if one of didn’t work. There are also plenty of human says he hasn’t seen many. He points to a its drugs caused problems in a pet study, diseases that pets don’t get, like prostate couple recent trials that used experimental FDA would never approve it for people. But cancer and Parkinson’s. Plus, researchers drugs to treat osteosarcoma that looked at the meeting an FDA representative said don’t have to spend months recruiting lab promising in dogs but fell short in people. that was not the case. “That was a huge win rodents, and they can give them a much Two other trials testing the antilymphoma for the field,” Khanna says. smaller dose of an experimental drug. That drugs GS-9219 and Zydelig proved safe Since then, NIH has become more in- makes pet trials expensive, as does the fact and effective in dogs, but toxic to humans. terested in these trials, too. In April, the that these studies—like those in people— “We’ve been so desperate for new drugs, National Cancer Institute announced that typically cover the cost of care and proce- especially for kids, we want to see prog- it would fund partnerships between veteri- dures, which can run into the thousands ress,” Baker says. “But that doesn’t mean narians, physicians, and scientists to bet- or tens of thousands of dollars, especially being blinded by our optimism.” ter understand the molecular biology of when dealing with cutting-edge therapies LeBlanc says there are signs that pet dog cancer. NIH also inspired the Ameri- like bone marrow transplants and radiation clinical trials can pay off. In 2013, for exam- can Veterinary Medical Association to cre- for brain tumors. “Doing a clinical trial in ple, FDA accelerated its approval of a drug ate its own version of ClinicalTrials.gov (a dogs is 10 times cheaper than doing it in called ibrutinib for lymphoma in people worldwide database of human clinical tri- als), which went online in June. And next year, the agency’s Comparative Oncology Sit. Stay. Heal. A sampling of pet clinical trials Trials Consortium—a network of 22 North American academic centers—will begin Researchers are conducting hundreds of clinical trials on dogs and cats across the world. releasing data from its largest pet clini- Here are a few that may have an impact on human health. cal trial to date, a 160-dog study of canine osteosarcoma, which LeBlanc is over- on August 12, 2016 TRIAL PURPOSE LOCATION seeing. “We want to get better data into Minibeam radiation Testing whether small, parallel beams of radiation can U. of Saskatchewan, everyone’s hands,” she says. for brain tumors treat malignant brain tumors in dogs. Saskatoon, Canada The field is also hoping for its first big GammaCore VET Testing whether a handheld electronic nerve stimulator U. of Georgia, Athens translational success. In 2015, New Haven, for seizures can treat epilepsy in dogs. Connecticut–based Kolltan Pharmaceuti- HER2/neu breast Testing an experimental vaccine against a type of Veterinary Oncology cals announced that its experimental anti- cancer vaccine breast cancer in cats that is also one of the most Services, Middletown, body drug KTN0158 dramatically shrank a aggressive in women. New York common skin tumor in dogs, prompting it to begin clinical trials in humans. “The dog Stem cells for dry eyes Testing whether an injection of stem cells from a Purdue U., dog’s own fat can restore the eye’s ability to tear. West Lafayette, Indiana trial had a dramatic impact on our strategy to develop this product for people,” says the http://science.sciencemag.org/ Photodynamic therapy Combining a drug with laser light to kill lung tumor Colorado State U., company’s president, Jerry McMahon. for lung tumors cells in dogs. Fort Collins He believes the main role of pet clinical Embolization for Testing whether blocking blood vessels in the U. of California, Davis trials in the future will be to help pharma- prostate cancer prostate gland can treat prostate cancer in dogs. ceutical companies like his minimize the risk of drug development. Instead of putting every Canine Testing two experimental U. of Minnesota, osteoarthritis pain anti-inflammatory medications. Twin Cities drug that works in mice into the human pipe- line, they can focus on the ones that help sick cats and dogs. “It makes the investment in Downloaded from humans,” Brown says, “but 10 times more after it showed promise in canine trials. And human drug development more promising,” expensive than doing it in rats.” because dogs are easier to operate on than he says. “It takes a while for things like pet Those are all big reasons it’s hard to get rodents, they have helped optimize ways clinical trials to become part of mainstream funding for these trials, LeBlanc says, es- to excise bone tumors in children without drug development, but I think they could be pecially from pharmaceutical companies. removing limbs. a powerful tool for the future.” “They want to get their drug to market as Still, LeBlanc admits that the field has Of course, there’s always the possibility soon as they can.” a way to go. “We don’t have a slam-dunk that pet clinical trials will never translate The government has also been loath to transition to better human health,” she says. to people, and that they’ll just help veteri- fund pet clinical trials because scientists “But I think that data is coming.” narians develop better drugs for dogs and know a ton more about rats and mice than cats. But many advocates don’t see that as they do dogs and cats, LeBlanc says. “NIH THERE ARE HINTS that pet clinical trials may a bad thing. “If we save these dogs, it has gets really uncomfortable with models that be edging into the mainstream. Last sum- an impact on every single family that owns haven’t been vetted in the same way as mer, nearly 200 and physi- a dog,” says Matthew Breen, a geneticist at mouse models.” That has forced veterinar- cians met for the first time with funders, North Carolina State University in Raleigh ians to scrounge money from their insti- government regulators, and representatives who has been part of more than a dozen tutions or from pet-centric organizations, from the pharmaceutical industry in Wash- pet studies. “When I get involved in these most prominently the Denver-based Morris ington, D.C., to discuss how these studies trials, it’s about helping the family. If we’re Animal Foundation, a nonprofit that claims could better contribute to human health. The helping the human or the dog, is there re- to have invested more than $100 million workshop, sponsored by the U.S. National ally any difference?” j

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Published by AAAS From bark to bedside David Grimm (August 11, 2016) Science 353 (6300), 638-640. [doi: 10.1126/science.353.6300.638]

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