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Canine connections

From cancer to epilepsy, dogs are informing human medical care—and vice versa

Batman is one lucky dog. Rescued from the streets of Berlin a decade ago and brought to the United States by Anna Brailovsky and Eric Baker, the laid-back Belgian shepherd mix seemed to be living a charmed life—until he had a massive seizure last July.

Alarmed, Brailovsky brought him to the veterinarian. There she heard words no pet owner wants to hear: Batman likely had a brain tumor that, left untouched, could kill him in a matter of weeks.

The veterinarian went through the litany of choices if an MRI proved the provisional diagnosis correct. A few years ago, their options would have been limited to watching and waiting while the disease progressed or humanely euthanizing Batman. But recent treatment advances provided another option: controlling the brain tumor through a combination of surgery and radiation therapy.

Still, this was devastating news for Brailovsky and Baker. Though they felt they needed to proceed with the MRI for their beloved Batman, they were concerned about the costs for a full course of treatment and the therapy’s potential side effects. The results of the MRI were disheartening, until an alert veterinary resident reviewing Batman’s file suggested an alternative and literally lifesaving plan that could make Batman a medical hero.

The resident knew that John Ohlfest, Ph.D., and College of Veterinary Medicine surgeon Elizabeth Pluhar, D.V.M., Ph.D., were looking for a way to test an idea. Ohlfest, who directs the gene therapy program in the Medical School’s Department of Neurosurgery, was exploring the use of a combination of gene therapy and immunotherapy to treat human brain cancer. The concept seemed sound, but before he could test it in people he needed evidence that it wasn’t harmful and could, indeed, curb cancer.

When Ohlfest attended a talk by a University of Minnesota veterinarian about cancer in dogs, he found that dogs suffered from cancers similar to those he was trying to cure in people. And he saw a perfect opportunity. Within a month, he and Pluhar had set in place a strategy for testing his ideas in dogs with brain cancer. Both scientists are members of the University’s Masonic Cancer Center, which fosters this type of collaboration.

Two-year-old Addison Baker offers a treat to Batman, his family's beloved dog. (Photo: Scott Streble)

“Liz Pluhar had something I didn’t, which was the ability to do surgery in dogs,” Ohlfest says. “And I had something she didn’t have, which was all the molecular biology and immunology that was required to do gene therapy and immune therapy.”

Ohlfest and Pluhar applied the therapy to Batman last August, surgically removing as much of the tumor as possible, making the remaining cells more sensitive to an immune attack with gene therapy and then administering a vaccine made from the tumor cells. The costs of the procedure were covered by research funds. Batman has been tumor-free ever since.

“It doesn’t take a brain scientist to say, ‘Wow! It’s probably worth treating more dogs,’” Ohlfest says.

And it has been. Including Batman, the team has treated five dogs, with very encouraging results that will ultimately benefit both dogs and humans.

Human trials?

“We’re already working on that,” Ohlfest says. “I think [our work with dogs] is going to accelerate the approval process.”

Understanding osteosarcoma

Dogs share our homes and our affection. At the University of Minnesota, they’re also sharing in the search for treatments and cures for conditions that ail us both.

Dogs are helpful for understanding the genetic origins of both human and canine cancer, says Jaime Modiano, V.M.D., Ph.D., a professor in the Department of Veterinary Clinical Sciences and director of the new Animal Cancer Care and Research program, run jointly by the College of Veterinary Medicine and the Masonic Cancer Center. This field of study, known as comparative oncology, provides valuable insights, Modiano says. Dogs share most genes with us (and come with pedigrees—useful for tracking genetic propensities), get the same cancers we do, live in the same places we do, and age faster than we do, so results come more quickly.

Jaime Modiano, V.M.D., Ph.D., consults with clinical pathology resident Sara Hill, D.V.M., on the results of a dog’s bone marrow sample. (Photo: Scott Streble)

Modiano’s research looks at how genes in tumor cells and normal cells differ. Being able to compare the genetic aberrations of human tumors with those of tumors from dogs of various breeds helps him determine which differences are related to the cancer and which are not. Last winter, he and Matthew Breen, Ph.D., of North Carolina State University, published research results showing that genetic changes in dogs with certain blood and bone marrow cancers are virtually identical to genetic abnormalities in humans diagnosed with the same cancers.

Modiano, whose lab is located in the Masonic Cancer Center, also investigates osteosarcoma bone cancer. When he joined the University of Minnesota last year, Modiano discovered that Subree Subramanian, Ph.D., assistant professor of Laboratory Medicine and Pathology in the Medical School, was exploring the genetics of osteosarcoma in humans. The two have since joined forces, studying the genes of tumor tissue taken from humans, rottweilers, golden retrievers, and greyhounds. The goals, says Modiano, are to “predict, prevent, and try to understand what we can do to decrease risk.”

Stopping seizures

In another collaboration, between University of Minnesota veterinary clinical sciences and neurosciences, faculty member Ned Patterson, D.V.M., Ph.D., was looking for better ways to help dogs with epilepsy when he encountered two researchers, James Cloyd III, Pharm.D., and Ilo Leppik, M.D., on the same quest in humans. A number of years back, Leppik had been interested in looking into alternative routes to administer levetiracetam, an anti-seizure drug. Patterson proposed testing new ways of using the treatment in dogs as a way to benefit both species.

John Ohlfest, Ph.D., teamed up with Elizabeth Pluhar, D.V.M., Ph.D., to save Batman’s life and test a new therapy that may someday be used in humans with brain cancer. (Photo: Tim Rummelhoff)

Doing so made sense for many reasons. Dogs get a natural form of epilepsy very similar, if not identical, to the disorder in humans. They’re closer to human size than are mice, so their response to medicines is more likely to match ours. And at the same time they’re informing human medicine, they’re potentially benefiting as well.

About one in four dogs with epilepsy will not experience relief with conventional care. “Many of my dog owners give up emotionally,” Patterson says. “Epilepsy is tough, so they sometimes give up and euthanize their pet.” Trying something experimental not only gives ailing animals a chance to get better, it also gives pet owners an opportunity to contribute to science.

So far the researchers have found that levetiracetam absorbs well in dogs and doesn’t cause muscle damage when injected into the muscle rather than given orally. They have begun to explore intravenous administration in emergency situations. Eventually, they hope to test other promising epilepsy drugs in dogs as well.

“At the veterinary college we’re trying to do more of these collaborations that benefit both dogs and people,” Patterson says.

Enormous potential

If your kidneys or mine fail, we could undergo dialysis to keep us alive. People in less developed countries rarely have such an option. To help cleanse the blood when kidneys can’t do it on their own, researchers are exploring the use of a bacterial culture, or probiotic, in the gut that can help rid the body of toxins normally removed by the kidneys. And to help them evaluate the treatment’s efficacy, David Polzin, D.V.M., professor of internal medicine in the College of Veterinary Medicine, is testing the probiotic in his canine patients.

“For the most part, these dogs are not going to get dialysis,” Polzin says, “so [this is] their sole option for furthering their treatment for advanced kidney disease.” He has been able to show that the bacteria don’t have an adverse effect on his patients. Further testing will help determine whether they provide a blood-cleansing benefit- information that could then be used to advance the same approach in humans.

Taking a similar tack, College of Veterinary Medicine assistant clinical veterinarian Kelly Hall, D.V.M., is testing a novel noninvasive device for measuring tissue oxygen levels in dogs to help guide therapies for shock, bleeding, and other trauma. She first heard about the device while attending a conference on critical care in humans where the developers of the device mentioned they were collaborating with Gregory Beilman, M.D., chief of surgical critical care in the Department of Surgery. Hall eagerly contacted Beilman to let him know she was interested in exploring its use with her canine patients.

“I see enormous potential in veterinary medicine,” says Hall, adding that the data she gathers from animals can be applied to humans, too.

In other studies, dogs are informing the understanding of human breast cancer and lymphoma as researchers gather information that can be used to improve veterinary approaches to the diseases.

“Where we are now is at the base of the mountain, and it’s a big climb,” Modiano says.

With dogs and humans traveling together as companions, that climb will be less arduous, and more successful, than it would be for either alone.

By Mary Hoff

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