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WHERE MEDICAL INNOVATIONS TAKE FLIGHT

New APS canine model enables better arthritis research

When APS scientists approached their company executives six years ago about initiating a new procedure for the study of arthritis, they first had to prove the project was worth funding internally.

After all, the research was to be paid for on APS’ dime, scheduled in around the projects of paying clients and completed through the time, talents and brainpower of a small APS team of scientists and technicians.

Fortunately, company leaders saw the project as worth the risk, which is why APS was recently able to release details of two studies that together propose a new model for medical device arthritis research utilizing dogs instead of rats. Now, APS is hoping the model can be optimized to help crack the arthritis code and get millions of people relief from their chronic pain.

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The studies are of significant interest to the scientific community because they will allow researchers to better measure the pain-relieving effects of arthritis-directed devices and medications, reports APS Chief Scientific Officer Jim Pomonis, who led the studies. That’s because the effects of arthritis pain and pain remediation are easier to measure in canines than rats, since canines tend to be more forthcoming and communicative with their responses.

“Time will tell how big this will be,” notes Pomonis of the study results. “That depends on how much it translates from pre-clinical research to clinical success. But if this ends up improving the quality and predictability of existing models, it will be a big deal.”

While data from the studies is available to other interested researchers, Pomonis predicts that in the near future the new testing procedure will be most widely used for contract research at APS, where the team is familiar with its tenets. That service should benefit both APS and its sponsors.

“There’s been a lot of interest,” he says. “It’s not groundbreaking, since we’re taking the same thing we did in rats and doing it in dogs. However, I think the elegance is in its simplicity. A lot of models in dogs are very complex, but we found making things simpler led to a clearer picture of how the disease progresses and is created.”

[Learn more about APS’ animal model offerings]

Fighting against arthritis

doctor talking with patient about pain in office

While Pomonis acknowledged the emotional element of working with dogs hasn’t always been easy, he believes it will be justified as part of the battle against the extremely pervasive OA. An additional consideration is that dogs frequently suffer from OA, and this model has drawn significant interest from animal health companies as they search for treatments for pets suffering from OA. That said, APS has strong standards about ethical animal treatment and continually works to reduce the numbers of animals needed for testing.

Pomonis noted that he’s long had an interest in finding new ways to address OA pain, primarily because this so-called “wear and tear disease” causes so much human suffering. Considered the most common form of arthritis, it already affects some 27 million people in the U.S. alone, most commonly occurring when bone-cushioning cartilage and other connective tissues wear out in the hands, knees, hips and/or spine. In the U.S., OA is estimated to cause knee pain in 10% of men and 13% of women age 60 and older. Other symptoms can include stiffness, tenderness, loss of flexibility, swelling, a sensation of internal grating and/or bone spurs.

Common treatments include over-the-counter painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), topical counterirritants, disease-modifying anti-rheumatic drugs (DMARDs), biologic response modifiers, corticosteroids, physical therapy or surgery involving joint repair, replacement or fusion, according to Mayo Clinic.

Unfortunately, OA is a growing problem in the U.S. due to the commonality of its risk factors.

It’s no secret aging baby boomers are skewing the population; the number of Americans 65 and older is slated to more than double by 2060, reaching more than 98 million to represent a full 24% of all U.S. residents.

Further, our level of obesity is problematic since extra weight adds stress to weight-bearing joints such as hips and knees, and proteins produced by fat tissue can cause harmful inflammation to joints. This year, the adult obesity rate exceeded 25% in 48 U.S. states. Nevertheless, even Americans who exercise to improve their health are at risk; joint injuries (including stress injuries) resulting from activity can increase the risk of OA.

Another contributor can be Type 2 diabetes, which seems to increase risk by raising the likelihood of obesity. By 2060, the number of U.S. adults diagnosed with diabetes is expected to nearly triple from 2014 numbers to reach 60.6 million.

Because OA is a degenerative disease that worsens over time, long-term effects can include chronic joint pain, stiffness, sleep disturbances and depression that can significantly affect quality of life. OA is also a contributor to multiple joint replacements, including many of the 680,150 knee replacements and 370,770 hip replacements logged in the U.S. when last measured in 2014.

Arthritis in all its forms reportedly costs the U.S. $128 billion in direct and indirect expenses.

Pushed forward by pain: Addressing global demand

woman with arthritis pain in her hands

Though APS doesn’t initiate its own studies on new drug therapies and devices, it regularly conducts its own applied research seeking new and improved methodologies for testing others’ inventions – often in conjunction with sponsors. For those projects, it chooses research areas that have a high likelihood of success and could offer significant assistance to the medical community.

“Like any other product offering you put out there, someone has to be willing to make some sort of investment — in both time and actual dollars,” Pomonis notes. “So you think big, assure yourself you’ve appropriately identified the value of your target, it then make sure it happens.”

The study of how to effectively and humanely further arthritis research using canine subjects was motivated by international demand for a better understanding of arthritis pain. For financial and humanitarian reasons, Pomonis explains, methods for curing the irreversible disease and/or finding better ways to alleviate its symptoms have been widely pursued by medical product developers in recent years.

“They’ve not had a lot of success curing the disease, so everyone’s looking for effective pain relief,” he noted. “If we had a pain drug that worked well in treating OA pain, we’d have a blockbuster on our hands.”

Not surprisingly, the global OA market is expected to grow at a CAGR of 8.1% in the next six years, increasing from $1.6 billion in 2016 to $3.5 billion in 2026, according to Globaldata.com. “The OA market provides an abundance of opportunities for the development of novel analgesics and disease-modifying osteoarthritis drugs,” states the report. “We anticipate with the rapid evolution of OA pipeline products, the OA market landscape will change radically over the next 20 years.”

Switching subjects: How dogs made a difference

Researcher reviewing data

Drawing on work he’d published before joining APS, Pomonis began working with another lead scientist (Veterinarian Dr. Allison Bendele of Boulder, Colorado) to design studies allowing researchers to stimulate, observe and potentially alleviate canine arthritis pain in the most humane way possible. The studies involved creating arthritic pain in the dogs by anesthetizing them, then either carefully severing tendons in their knees or simulating OA with an injection of monosodium iodoacetate (MIA). Either a placebo or carprofen, a well-characterized NSAID,-were administered, and then the subjects were guided through a series of exercises to gauge their performance and response. The animals with OA showed deficits in their abilities to perform the exercises, but this was significantly restored after carprofen was administered. Pathology and histopathology followed.

“We really don’t understand what causes the pain in OA,” says Pomonis. “This may be another model for us to begin to understand the biology of the disease and the pain.”

Traditionally, scientists have used rats for similar studies; however, he notes, they are not ideal for many studies because rats are limited in how they can respond to and show different levels of pain.

“Dogs and rats are very different in how they exhibit pain behavior,” he says. “Because in the wild, rats, as animals, are preyed upon, so they manage to hide their pain, sickness or discomfort so they’re not picked off by a hawk. With dogs you can tell when they’re hurting … they’ve very demonstrative with their pain and get to the point where they’re emotional. They’re much more human in this behavior than the rats or other typical research species.”

In essence, the studies identified a new and reproducible way for scientists to effectively study pain responses as they work to develop better arthritis therapies — or even maybe a cure.

Looking to a healthier future

Since the study results were published, Pomonis notes he’s presented findings at several science-oriented meetings.

“We’re always looking at things that will continue to add value to sponsors,” he says. “This also has the chance to bring new developing drugs or device mediated treatment modalities into the clinic. I feel good about where this is going.”

Contact us to learn how our new canine model and other offerings may help further your research.

At American Preclinical Services, we can offer you extensive experience in veterinary science, medical device research, toxicology, pharmacology, histopathology, FDA and ISO quality assurance and regulatory policy.

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