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Kneedy

The future of arthritis care

Jimmy Cook

Veterinary researcher Jimi Cook’s lab can create biologic joint replacements for humans and animals. Luckily, dog Chula doesn’t need Cook’s high-tech services. Photo by Rob Hill

Arthritic joints, especially knees, hobble millions of Americans and cost billions in treatments that yield so-so results. No cure exists. Or does it? Now MU researchers including Jimi Cook are poised to offer a new treatment that could revolutionize arthritis care. But who will pay to launch this cure from lab to market, who will reap the profits, and how much will patients have to pay for the privilege of movement?

By age 5, a time of life when most of us are sure we’re invincible, Jimi Cook knew a lot about vulnerability, especially when it came to knees.

Back then he couldn’t have known that in 2010 surgeons would perform about 500,000 total knee replacements (TKRs), that such procedures would account for 8.2 percent of Medicare payments, and that by 2015 hospital charges for TKRs could total $40.8 billion. He didn’t know he was on the heels of the Baby Boomer generation, a group whose athletic and overweight members alike would rub enough knees the wrong way to send the number of TKRs skyrocketing to 3.48 million by 2030.

But he did know for sure that his grandfather was hurting.

“My grandfather helped raise me,” says Cook, a researcher and orthopedic surgeon at MU’s College of Veterinary Medicine. “He had severe osteoarthritis of the knees and was one of the first people in the United States to have knee replacement surgery. In fact, he had six knee replacement surgeries because they never worked very well. Because of his knee problems, we exercised together by riding bikes.” And movement was at the center of life for Cook, who went on to water ski professionally. “Eventually, my grandfather was limited to walking with canes and spent some time in a wheelchair.”

Cook’s Comparative Orthopaedic Laboratory team and its collaborators are on the cusp of delivering what he calls “the Holy Grail of arthritis treatment.”

Even as a lad, Cook knew he would somehow learn to help people with knee problems. Current treatments for joint problems are palliation — various methods of soothing symptoms, he says. “Palliation is not bad, but my goal is to cure joint disease. The passion behind it for me is to do better than what my grandfather had.”

Cook’s Comparative Orthopaedic Laboratory team and its collaborators are on the cusp of delivering what he calls “the Holy Grail of arthritis treatment.” Their quest is for a biological knee replacement, a living lining of bone and cartilage that the team grows in the laboratory.

In the O.R.

The prospect of the biological knee replacement is tantalizing to surgeon Jim Stannard, who collaborates with Cook and directs the Missouri Orthopaedic Institute. Before coming to Mizzou in 2009, Stannard worked in Birmingham, Ala., and had one of the largest practices in the country dedicated to repairing severely damaged knees. “I already can reconstruct almost any ligament you can tear and even transplant a meniscus if you tear that. But what we haven’t been able to handle is the lining on the end of the bone. It’s called articular cartilage. It’s a thousand times more slippery than wet ice. That’s why a healthy joint can move all day long. Arthritis occurs when you wear through that cartilage down to bone. It’s like throwing gravel on the ice.”

Surgeons can repair small areas of damaged articular cartilage using cartilage grafts from donors. But: Only if the donors died recently enough, they are the right size and the cells are still alive. “It’s pretty neat, and it beats the heck out of doing nothing,” Stannard says. But: He tells patients that a knee with grafts is akin to a 50,000-mile tire that’s already got 45,000 miles on it. Similarly, metal-and-plastic knee replacements can be a big improvement over an arthritic joint. Another but: “An enormous number of people with knee problems still want to jog and play tennis — things you shouldn’t do with metal-and-plastic knees. You just rip them up,” he says.

Cook’s biological knee replacement is way past all that, Stannard says, describing the results with phrases such as “fully functioning” and “good as new.” 

Don’t sell your ibuprofen stock just yet, though. There’s a hitch.

Sole custody of the joint 

So far, you’d have to walk on four legs to get this treatment. Cook has performed biological knee replacement surgery on animals, including rabbits, horses and dogs. The new treatment has yet to win FDA approval for use in humans, a step that likely will take five years and $15 million in further research to overcome. The source of the money could influence how long approval takes and how much the treatment costs in the end. 

“At the moment, Dr. Cook’s lab is the only place that makes biological knees,” Stannard says. “The potential to be the world’s leading center for this procedure is real, and the determining factor is not whether he can produce the biological knees or whether I can do the surgery, it’s whether we can get past the FDA.” 

Making a new knee


1. MRI data of an arthritic kneecap are used to create a virtual mold and a virtual patella to make actual molds of the replacement kneecap.


              knee 


2. The biologic scaffold is created using an “organ printer” and placed in a stainless steel mold.

                                                                     knee 


3. Cartilage cells are injected into a “biological jello,” which is then injected into the mold. New cartilage grows in three weeks using special culturing methods.


              knee 


4. A surgeon can remove the arthritic surface and secure the living biologic joint.

                                                                     knee 

The next medical steps look like this: After the FDA is satisfied that the biological knees have performed well in animals, Mizzou could begin a year of safety trials in humans to show the treatment does not harm patients. “During that time, MU would be the only place on the planet a patient could get a biological knee,” Stannard says. Then a clinical trial lasting five years or so could begin. This expensive and rigorous study would compare outcomes of patients randomized to Cook’s biological knees or to the graft treatment mentioned previously. This research would scrutinize not only the surgery but also its aftermath as the study follows patients through rehab and assesses their function for four years or so. 

The route to pay for the research is less certain. “We could apply for federal grants, but that might take a couple of years,” Stannard says, and other labs might catch up. “Or, we could partner with a big corporate firm that would pay for it. We’d license it to them, and when it goes to market, they will want to charge as much as the market will bear, which may limit who gets it.” 

The researchers prefer door No. 3, where Mizzou comes up with the money. “That’s how we could maintain control of it ourselves,” Stannard says. “Wouldn’t it be great to steer this thing so that a company doesn’t charge twice as much as a metal-and-plastic knee just because they could? It’s not that expensive to grow the biological joints. Our goal is to bring it to the masses. If we can fund the next step, we could name the operation Tiger Orthopedics. People would be flying in from all over the world for a biological joint.” 

Achieving bony prominence

When Cook finished his doctorate in 1999, it was a new idea to dedicate a lab to research on orthopedic problems common to animals and humans. A handful of labs were trying it out in a small way. Being a veterinarian made the crossover even more difficult. “Back then there were some leaders of orthopedics companies and orthopedic surgeons who would say, ‘How can your work apply to humans — you’re just poodle groomers.’ ” 

Meanwhile, Cook was reading scientific literature on both human and animal orthopedics. “I’d see two articles — canine ACL injuries and human ACL injuries, for example — and know we could apply work from the human side to our patients. But I also knew that, if we could build bridges, we could apply our work in animals to humans. But not many people were even talking about that link. It’s really just a communication gap. Veterinarians and physicians speak slightly different dialects of the same language, but until you get those dialects together, the conversations never happen, and they’re just parallel paths that should converge but don’t.” 

Luckily, Keith Kenter, MD ’90, an orthopedic surgeon formerly at Mizzou, was open to collaboration. “He’d come over to observe our surgeries, and I’d see his surgeries in humans. In arthroscopy, once you’re inside the joint, it all looks the same. I’d say ‘That could be a dog on your screen.’ We both saw how comparative orthopedics could benefit all our patients — the two-legged and the four-legged.”

One day in 1997, Cook and Kenter went to a restaurant and charted a course for the Comparative Orthopaedic Laboratory. “We wrote everything out on a napkin and built it from there. We wanted to really make a difference in medicine,” Cook says. The lab’s staff of 25 includes graduate students and faculty researchers from veterinary medicine, human medicine, engineering, biochemistry and physical therapy. An annual budget of $1.3 million covers salaries and basic expenses. Dozens of projects run at any given time in three areas: diagnosing disease; understanding disease mechanisms; and developing treatment options, including regenerative medicine, such as the biological knee. 

Jimmy Cook

In 2001, researcher Jimi Cook chats with his late grandfather (and inspiration) Robert Gordon.

Stannard, like Kenter, is collaborating with Cook, who has an office a few doors down the hall in the Missouri Orthopaedic Institute. Stannard also directs the MOI, which is key to bringing biological knees to patients as quickly as possible. The institute is a new hospital on the University Hospital and Clinics campus. Typically, a leading lab like Cook’s does the basic science and some testing in animals but then must go elsewhere to find physician collaborators for human studies. That’s awkward, the transition can be slow, and the arrangement is not conducive to good communication between lab and clinic. 

“Some labs do great work, and some institutions have great clinical facilities,” Cook says. “But we have a close connection between lab and clinical professionals, and we’re just minutes apart. We talk to big medical companies about new treatments all the time. When they see Dr. Stannard and me in the same room interacting the way we do, and when they find out we talk every day and work shoulder-to-shoulder to improve patient care — they say Mizzou Orthopaedics is like nowhere else in the world.” 

Despite barriers ahead, Cook sees the biological knee coming to fruition. “I get e-mails every day from around the world asking, ‘How can I get a biological joint?’ And I say, ‘Just hang on — we are working hard on it.’ ”

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