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Biotechnology and health

Your Pet’s Disease Could Be Cured by Gene Therapy

Genetic medicine isn’t just for people with life-threatening diseases—pet dogs are now being treated with it, too.

Courtney Seymour had long considered her dog Greta, a nine-year-old chocolate and white boxer, an essential part of her family. So when Greta was diagnosed with degenerative myelopathy, an ailment that, like its human counterpart Lou Gehrig’s disease, causes paralysis and an inevitable painful death, Seymour was devastated.

Then came a sliver of hope from one of medicine’s most promising—albeit radical—new therapeutic approaches to genetic diseases. Seymour’s vet mentioned that a study at Tufts University was recruiting pet dogs with the disease to test an experimental treatment called gene therapy. Though there is no certainty of success, Seymour sprung at the chance, driving 150 miles from her home outside of Albany, New York, to Grafton, Massachusetts, so Greta could receive the treatment in March.

For decades, gene therapy has been envisioned as a way to cure disease by introducing new genetic material into people’s DNA. The technology is finally showing success in patients, with treatments moving closer to regulatory approval in the U.S. (see “Gene Therapy 2.0: 10 Breakthrough Technologies 2017”). Some of these therapies were first tested in research dogs, which have immune systems similar to humans and get many of the same diseases. But as humans seek better medical care for their furry family members, these therapies could soon be on the market for pet dogs, too.

Dominik Faissler, a veterinary neurologist at Tufts University who is leading the trial, is studying gene therapy for canine degenerative myelopathy with the goal of eventually helping people. He and his collaborators at the University of Massachusetts Medical School have so far treated five pet dogs with the disease, including Greta, and plan to treat five more in a small pilot study.

A mutation in the SOD1 gene has been linked to the disease in dogs, and an error in the same gene is associated with amyotrophic lateral sclerosis, or Lou Gehrig’s disease, in humans. The treatment researchers developed is a single spinal fluid injection of a modified virus that can infect the nervous system. The virus is engineered to deliver genetic material that turns off the expression of the faulty gene. Faissler hopes the therapy could be advanced into human clinical trials if it is effective in dogs. 

Faissler says the therapy appears safe in dogs so far, but it’s too early to know whether it will halt or reverse the disease. It may take months for the therapy to have an effect, and Faissler says it’s possible that dogs will have to be treated earlier to benefit.

Researchers are also using gene therapy to treat dogs with hemophilia, a bleeding disorder in both canines and people that’s caused by a genetic mutation. In hemophilia, a mutated gene means the body can’t produce enough of a protein that clots blood. Gene therapy, like the one being developed by Valder Arruda’s team at the University of Pennsylvania, uses a modified virus containing a correct version of the gene that codes for the clotting proteins.

Arruda’s team started treating pet dogs with hemophilia in 2012 at no cost to the owners. “After many years of treating research animals, we began to discuss whether we should extend the treatment for pets,” Arruda says. “This is sort of closing the circle. We started to experiment in dogs to help us to develop treatments in humans and now this is back to dogs.”

So far, Arruda and his colleagues have treated four pet dogs with hemophilia A and a fifth dog with hemophilia B. One dog owner even traveled from Athens, Greece, for the treatment. This month, the research group will give a sixth dog the therapy. Some of the dogs’ clotting activity has reached 90 percent, meaning they only have minor bleeds from time to time. All of the pet dogs that have received the therapy are still living.

In general, dogs are living longer, and that means they are more prone to age-related diseases, including cancers. In fact, a type of gene therapy for dogs is already on the market to treat melanoma. Called Oncept, it’s known as a DNA vaccine. It contains a human gene that makes a protein found on melanoma cells. The dog’s immune system recognizes the human protein as foreign, triggering an immune response against the canine melanoma cells that display a similar protein. About 60 percent of dogs with melanoma benefit from it.

Bruce Smith, a gene therapy researcher at Auburn University in Alabama, in collaboration with the University of Washington, St. Louis, and the Institut Pasteur in France, is working on a type of gene therapy called an oncolytic virus for osteosarcoma, a type of bone cancer with a poor prognosis. It occurs commonly in dogs but less frequently in humans.

The therapy is a modified virus that is designed to spread throughout the body and preferentially infect and kill cancer cells. As the infected cancer cells self-destruct, they release new infectious virus particles to help destroy the remaining tumor.

In an initial study of 16 pet dogs, the therapy was shown to be safe. But animals that received the therapy didn’t live longer on average than those that just received the standard care. That was disappointing to Smith, but his team is working on improving the therapy to make it more effective.

The longest surviving dog was a little over two years, better than the average survival of a year for dogs with this type of cancer. “Unlike treating a 60-year-old human, where we want them to live to 90 and we have to figure out how to get them 30 more years, in veterinary medicine we’re only thinking about maybe how to get an additional three to five years if it’s an old dog,” Smith says.

Smith is confident there’s a canine market for cancer gene therapies like Oncept and the one his team is developing. He says the quality of medicine for pets is improving at a fast pace, and cancer is a major health concern for owners of older dogs. “Dogs are members of the family now. People think of them as their children. When it’s your family member you want them to be treated the same way you’re treated,” Smith says.

One question that remains though is how much these novel therapies will cost. The price of Oncept runs about $3,000 for a series of four shots. But potentially curative therapies for inherited diseases are likely to have much higher price tags. Strimvelis, a human gene therapy approved in Europe for an inherited immune disease, costs more than $600,000

Meanwhile, the fate of Seymour’s beloved pet remains uncertain. Despite the gene-therapy treatment, Seymour hasn’t noticed an improvement in Greta’s condition but is holding out hope. “Whether the progression has been slower than it would have been without the treatment, I can't say,” she says.

Regardless, researchers say pets like Greta are playing an essential role in the development of the technology. And eventually the reward could benefit both people and their best friends. “I believe gene therapy in people and gene therapy in pets will go hand in hand,” Faissler says. “I feel this is the treatment of the future.”

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