When Spanky and Darla, two English bulldog puppies, came to the University of California, Davis, in early 2017, the two were unable to wag their own tails. They limped along, stumbling and licking, their hind legs dragging on the floor uselessly behind them.
The pair had both been born with spina bifida, a birth defect that occurs early in animal and human pregnancies. With spina bifida, the neural tube of an embryo fails to properly form within the first 28 days of gestation, resulting in a small hole in the spine as the embryo grows. In humans, this usually results in multiple, permanent medical complications when the baby is born, including hydrocephalus, Arnold Chiari malformation, and clubbed feet. In bulldog puppies, who are more susceptible to spina bifida, this results in hind-leg paralysis and incontinence. While most puppies with spina bifida are euthanized after birth, human babies born with spina bifida acquire hundreds of thousands of dollars in costs over the course of their lifetimes to manage this condition, according to a recent study published in the American Journal of Preventive Medicine.
But rather than euthanizing Spanky and Darla, the two were taken to the Veterinary Institute for Regenerative Cures at UC-Davis to take part in a revolutionary new treatment. The puppies would receive surgery from Dr. Beverly Sturges, a veterinary neurosurgeon at UC-Davis, who was part of a team with Dr. Diana Farmer, chair of the department of surgery at the UC-Davis School of Medicine. During surgery, Sturges placed a stem cell treatment made up of placenta-derived mesenchymal stromal cells, or PMSCs, on the damaged part of the bulldogs’ spines. In theory, the stem cells would help the puppies’ nerves regenerate, gaining them back at least some of their hind-leg and bladder control. Previously, the research team had induced spinal cord injuries in fetal sheep and had used the stem cell treatment to repair them, with good results: After birth, the sheep could walk and run with no evidence of a spinal cord injury. The team was hoping that Spanky and Darla would be able to do the same.
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UC-Davis is unique in that its Veterinary Medical Teaching Hospital and its School of Medicine form a collaborative effort in treating disease, not only with spina bifida, but for other ailments like cancer, diabetes, and vascular conditions that affect humans and animals alike. What benefits one species, they reason, will likely benefit the other.
“Our collaboration starts with individual faculty members reaching out to their counterparts in the School of Medicine, or vice versa,” Dr. Dori Borjesson, director of the Veterinary Institute for Regenerative Cures, said. Their department is often approached by doctors who can’t treat humans just yet without FDA approval, so they approach Borjesson and her team to find out what they’re working on. What they offer is the unique opportunity to provide innovative treatment strategies for human beings using what they’ve learned from cats and dogs. “We can start a clinical trial with animal patients because it’s easier to do than in humans,” she said. “Sometimes we find things in the animals and we’ll say, ‘We’re seeing amazing success with these types of cells treating this disease—can you help us find someone to start a clinical trial in people?’”
Since the 18th century, biomedical researchers have used rabbits and mice to investigate cures for human disease. But increasingly, scientists are realizing how limited they are when it comes to understanding diseases in humans.
“If you want to induce renal failure in a rabbit or a mouse, you ligate blood flow to the kidney,” Borjesson explained. “That’s a model of kidney failure, but taking a rodent and ligating its artery for a couple days has nothing to do with how kidney disease develops in people or pets. So it’s no surprise that research done with those animals doesn’t translate well into human medicine.”
The physiology of disease in people and companion animals like cats and dogs, however, is “remarkably similar,” Borjesson said. And the same diseases—cancer and spina bifida—occur naturally in humans and companion animals, where in laboratory animals they need to be induced. Furthermore, companion animals and human beings share genetic similarities that laboratory animals like mice and rats don’t. Cats and dogs are also both exposed to various environments and diets, resulting in a more representative model for human disease.
Research with companion animals is unlike research with laboratory animals in one other crucial aspect: The research is geared toward healing animals, rather than experimenting and then destroying afterward. And because companion animals are so fiercely beloved by society, researchers have had to contend with some myths.
“People think about it like we’re killing beagles or something,” Borjesson said. “But we don’t take healthy dogs and make them sick. We’re putting dogs in clinical trials who have a disease and the owners want it fixed.”
Dr. Boaz Arzi is another surgeon currently working toward curing a disease that affects pets and their owners. Arzi works with cats who have developed feline chronic gingivostomatitis, or FCGS, a severe and chronic inflammation of oral tissues. Using what he’s learned from his current clinical trial in the Veterinary Institute for Regenerative Cures, he hopes to treat a similar human disease called oral lichen planus, which results in painful oral ulcers.
“There’s no real ideal cure,” Arzi says, of FCGS. “Typically cats have to go under full extraction [of their teeth], but that doesn’t solve the problem. You have about 30 percent of cats who don’t respond to therapy at all.” In the lab, Arzi and his colleagues have developed a stem cell therapy that is given to the cats intravenously as part of the clinical trial. The stem cell therapy “jump starts” their immune systems and drastically reduces swelling. So far, the results are promising.
“With autologous stem cells, we are approaching a 70 percent response with substantial improvement, almost completely cured,” Arzi says. “Obviously it depends on our funding, but we see this moving forward to human trials.”
Farmer has high hopes for her spina bifida treatment as well: At the four-month, postoperative checkup, Darla and Spanky were able to run and play like typical puppies, seemingly free of the debilitating paralysis that plagued them just a month earlier. Within the next year, Farmer plans to file a request with the National Institute of Health to start a clinical trial of the stem cell treatment in human fetuses with spina bifida. Like the puppies, her hope is that children born with spina bifida will be able to enjoy a life free of wheelchairs and walkers. It’s too early to tell if the treatment will be a success in human beings—but if it is, we’ll have puppies like Spanky and Darla to thank.
