春水堂视频

New study looks to second generation of novel gene therapy as a way to help dogs with joint pain

When dogs develop osteoarthritis, their demeanor changes drastically. Instead of eagerly getting ready for walks, gleefully tossing around toys and excitedly greeting their humans at the door, dogs with this progressive, joint degeneration disease become listless, lethargic and, at times, irritable.

The painful condition makes life difficult for dogs, but it鈥檚 also heartbreaking for their owners, who have few options for relieving their beloved pets鈥� discomfort. Now, a novel gene therapy developed at the University of Colorado Boulder is bringing joy back into the lives of pets and their humans.

鈥淚t鈥檚 very striking,鈥� said Linda Watkins, CU Boulder Distinguished Professor in the Department of Psychology and Neuroscience. 鈥淚t鈥檚 not just helping the dogs, but when you start talking to owners, they lost their family member. They don鈥檛 play anymore or want to go for walks because it hurts so badly. They鈥檝e lost their doghood. And this therapy brings that back. All the things you think of with a happy dog, that comes back again, and owners are so thrilled.鈥�

Watkins and Broomfield veterinary pain specialist Dr. Rob Landry are recruiting dogs with severe osteoarthritis (and their owners) to help test the second generation of a non-viral gene therapy in the hopes of moving the improved therapeutic toward a federal veterinary clinical trial.

Dogs that are accepted into the double-blind study must be able to visit Dr. Landry鈥檚 veterinary hospital regularly for several months for evaluations and assessments. Participation in the study is free, but owners must pay for an initial consultation to determine the dog鈥檚 eligibility or already have an osteoarthritis diagnosis and X-rays.

Dogs in the control group will get a placebo. However, after the initial study period ends, their owners can opt-in to receiving the free therapy as well, Watkins said.

Nature鈥檚 anti-inflammatory

Osteoarthritis develops when cartilage鈥攖he flexible connective tissue that helps cushion the joints鈥攂egins to break down, either because of injury, disease, repetitive use, age or some combination of factors.

This deterioration causes progressively worsening inflammation, which leads to pain, discomfort and decreased mobility. Prolonged inflammation, in turn, leads to further deterioration.

The condition is common among senior dogs and large breeds, but there鈥檚 no known cure. It can be so painful and debilitating that some owners opt to euthanize their dogs to end their suffering, Dr. Landry said.

The gene therapy drives the production on a natural protein called Interleukin 10, or IL-10, which the body produces to dial back its own inflammation response to an injury or infection.

鈥淭his is nature鈥檚 own potent anti-inflammatory,鈥� said Watkins, who co-founded the biotechnology company to further develop the therapy.

During an initial study at the , Dr. Landry skillfully injected a solution containing circular DNA molecules directly into dogs鈥� osteoarthritic joints, where it instructed cells within the joint to produce more IL-10, thus reducing inflammation.

In that first round, Watkins and Dr. Landry tried the gene therapy on more than 40 Colorado canine companions, from Siberian huskies to golden retrievers to mixed-breed dogs. They got good results, which led to the launch of human clinical trials for osteoarthritis underway in Australia and California.

After the treatment, participating pups could more comfortably walk, run, go up and down stairs and stand up. Their owners also reported improved quality of life and less pain.

鈥淭he dogs are happier and far less dependent on medications,鈥� said Dr. Landry, who is also an adjunct professor in the CU Boulder Department of Psychology and Neuroscience. 鈥淚t鈥檚 amazing research. It鈥檚 made impacts on people鈥檚 lives for sure, and pets鈥� lives without a doubt.鈥�

Testing the second-generation therapy

Now, they鈥檝e tweaked the therapy and believe the new version will 鈥渃ome on stronger and last longer,鈥� Watkins said. After years of delay caused by the coronavirus pandemic, they鈥檙e ready to begin testing the second generation of the therapy on dogs.

鈥淔or IL-10 to do its thing, to be an anti-inflammatory, it has to bind and signal鈥攊t has to talk to the other immune cells and tell them to calm down in order to work,鈥� she said. 鈥淲e鈥檙e now encoding not just IL-10 but also giving it this signaling component. We鈥檙e making the Il-10 signal much better so it can do its job better.鈥�

With the results of this second dog study, Watkins and Dr. Landry hope to gain approval from the veterinary arm of the for testing the second-generation therapy in canine clinical trials.

After that, they hope to see widespread adoption of the therapy in veterinary practices across the country.

鈥淥wners should think of this as trying to help their own dog, but it鈥檚 also for the greater good of dogs鈥攖hey can be part of something that can move into an FDA clinical trial to make the world a much better place for dogs with osteoarthritis,鈥� Watkins said.