Dr. Matlock Jeffries is exploring novel ways to bring relief to people with arthritis
Just about everybody knows – or is – someone with osteoarthritis.
An estimated 32 million Americans live with OA, including more than half of those over 65.
“It’s the most common cause of disability in the U.S.,” says OMRF’s Dr. Matlock Jeffries, a board-certified rheumatologist who has studied the condition for more than a decade. Yet, he says, “We don’t currently have any osteoarthritis-targeted drugs.”
Osteoarthritis stems from the loss of cartilage between bones and joints. The knee is the most frequently affected, and the only definitive treatment, joint replacement, is the leading expense for Medicare each year. In total, the National Institutes of Health estimates that the condition levies an annual economic burden of more than $130 billion on the nation’s economy.
Despite its toll, there’s no treatment to slow, stop or reverse OA, and doctors can’t predict its development or progression. Jeffries wants to change that.
During medical school at the University of Oklahoma Health Sciences Center, he worked as a research technician in an OMRF lab focused on lupus epigenetics, or how external factors can cause changes in how genes work. It set Jeffries on a path to specialize in internal medicine and rheumatology, where he imagined he would study and treat autoimmune conditions that affect the joints, muscles and ligaments.
Early in his residency, the physician-scientist realized that his patients “all had OA.” When he dug into the medical literature, he found little research on the condition. “With how common it was, I thought that was strange. I wondered if we could do what we were doing with lupus and look at the epigenetics of OA,” he says.
The question gave birth to the dual focus of Jeffries’ career. Today, he treats patients with OA in OMRF’s Rheumatology Center of Excellence. In his lab, he studies both the epigenetics of the disease and how it is linked to changes in our microbiome, the trillions of tiny organisms that live throughout our bodies. He does it using a unique strain of mouse called a “superhealer.” These rodents naturally (and unusually) heal wounds to their ear cartilage, which resembles knee cartilage.
Jeffries transplanted microbes taken from the gastrointestinal systems of the superhealer mice into a group of mice with average healing capabilities. After the transplant, the non-healer mice were protected from developing OA, as were their offspring. The results, which Jeffries says were “completely unexpected,” indicate the gut microbiome has more influence on the body’s immune response to injury than previously understood.
To guide their next steps, his lab is now working to understand whether certain bacteria lead
to that ability to heal or if it’s linked to an overall change in the microbiome after an injury. Time will tell whether a whole microbiome transplant or simply a strong probiotic cocktail could yield the same results in humans.
Still, Jeffries says this particular path shows potential for the treatment of post-traumatic OA, which develops following an injury to a joint like a ligament tear. This form of the disease accounts for an estimated 3 million OA cases and is one of the top reasons for injury-related discharge among active-duty U.S. soldiers. “Potentially, if an injury was caught early enough, we could change someone’s outcome,” he says.
For Jeffries and others seeking to develop new treatments for OA, clinical trials represent a major obstacle.
Researchers conduct clinical trials over a relatively short period of time, with even the longest phases typically spanning no more than a year or two. During this time, they’re able to observe the benefits (or not) that come from a new form of treatment.
However, in osteoarthritis, this timeline would be stretched substantially. Disease progression can occur over a span of decades, and, says Jeffries, “It’s really not feasible for a clinical trial to last 10 years for Phase I, 10 years for Phase II, and have it take 40 or 50 years for a new drug to come to market.”
For effective OA trials, he says, “What we really need is the ability to identify patients who are likely to experience rapid disease progression.” In 2022, his research team published a study of knee and hip OA showing they could find these patients with a single blood draw.
OMRF has filed a patent on the technology and is currently seeking an industry partner to develop it. The hope, Jeffries says, is that the discovery will enable the completion of clinical trials for OA treatments in the span “of a few years instead of a few decades.”
Meanwhile, in the ongoing search for new therapeutics for the condition, research volunteers represent another critical piece of the puzzle. “Patients who are willing to donate samples are the only way forward,” Jeffries says. “We can’t make progress without them.”
To continue his work, Jeffries relies on patient volunteers like Oklahoma City’s Roberta Roush. Roush’s doctor diagnosed her with knee OA in 2021 at age 59. She still runs an average of 20 miles a week, but after watching her father undergo two OA-related knee replacements, she wanted to do her part to advance research on the condition.
When she saw an ad for one of Jeffries’ OA studies, Roush called right away to see if she qualified. “They made it so simple,” she says. “It was a no-brainer to get involved.”
Roush visits OMRF every six months to give blood, saliva, and microbiome (stool) samples, and take a single X-ray. All in, she guesses the process takes about an hour twice a year. And even though OMRF compensates her for her time and effort, Roush prefers to donate the money back to the foundation. “It’s an honor to participate,” she says. “I’m just happy to help.”
Read more from the Winter/Spring 2024 issue of Findings