Getting the jump on osteoarthritis

COLUMBIA, MO — A group of researchers is exploring ways to diagnose and treat osteoarthritis in the earliest stages, before irreversible damage is done to joints.

James "Jimi" Cook, DVM, PhD, is leading a group at the Comparative Orthopaedics Laboratory (COL) at the University of Missouri Department of Veterinary Medicine in Columbia, Mo., in the effort. COL was founded in 1998 by Cook and Keith Kenter, MD. The COL team is diverse and includes veterinarians, physicians, engineers, biochemists and pathologists.

"The goals of the COL are to find ways to promote joint health and better diagnose, treat and prevent joint disease in people and animals," Dr. Cook says.

Osteoarthritis in animals and humans

Osteoarthritis is a chronic degenerative joint disease involving both soft and bony tissues. The causes include trauma, infectious processes, congenital abnormalities or immune system responses. Osteoarthritis can affect dogs, cats, horses, birds, even guinea pigs. Some estimates place the incidence as high as 20 percent in all cats over the age of 12 years and, in some dogs, especially the larger and rapidly growing breeds, the incidence of osteoarthritis can approach 75 percent.

In humans, osteoarthritis is one of the leading causes of disability. More than 20 million people in the United States are affected, and most adults over the age of 50 display some symptoms. It is projected that as the baby-boom generation ages, the number of cases of osteoarthritis stands to increase dramatically.

Cook and his team realized that for all patients — animal and human — no treatment for osteoarthritis is anything more than palliative because the diagnosis is usually made later in the course of the disease, after the patient has already been experiencing significant pain in the joint. By that time, damage to the joint is usually irreversible.

"In theory, and based on basic science, there is a stage of OA that is reversible," Cook says. "We decided to say, 'Is there any way through all the technology and methodology we have available we can diagnose OA in the reversible stage?'"

Study findings

Because osteoarthritic changes manifest in dogs within the span of a few weeks, Cook and his team developed a three-month study of 12 dogs they knew were statistically likely to develop osteoarthritis. Using clinical assessments, MRI and arthroscopic examinations, and laboratory testing such as histology, biochemistry, and gene expression analysis, complete examinations of the study animals were performed during weeks one, two, four, eight and 12.

Cook tells DVM Newsmagazine that changes in specific genes' expression occurred as soon as two weeks after the insult that would eventually result in clinical signs and symptoms of osteoarthritis, even though at the time of gene expression measurement the animals were completely asymptomatic.

"We find the abnormal gene expression at two weeks, then definitive MRI changes associated with osteoarthritis at eight weeks. Then we go back to the two-week MRI to see if we can tease out changes that may be predictive of arthritis at those early stages," Cook says.

The team's findings were confirmed by further tests on other groups of dogs, and the most recent testing of approximately 50 animals will be concluded by the end of this year.

Next steps

"We have enough information that companies are interested to test drugs already. We're seeing if we can evaluate effectiveness of drugs earlier in the process," Cook says. "We have a long way to go, but everything has been really positive so far."

Cook plans to apply for grants from the National Institutes of Health (NIH) to conduct further tests in animals and, eventually, humans. He anticipates the entire research to take five to 10 years to complete.

Cook credits his team at the COL with the success of their work so far.

The team members include COL associate directors Derek Fox, DVM, PhD, and Jim Tomlinson, DVM, MVSc; Aaron Stoker, PhD, molecular biologist; William Carson, PhD, a specialist in biomechanics; imaging specialist Cristi Cook, DVM, MS; research specialists Mary Cockrell and Donna Whitener; and administrative assistant Linda Salmon, along with 22 others from various departments. The COL enjoys a strong working relationship with the Department of Orthopedic Surgery at the University of Missouri Medical School.

"This is a great team; everyone is motivated for the right reasons," he says. "We go around the room and ask, 'What problem couldn't you solve today? What couldn't you explain to a patient today? What frustrated you today?' We found a recurrent theme, that we were all tired of just palliating arthritis. That's not good enough, and we want to do better."

Cook remains committed to the value of his work for his veterinary patients.

"Our work is on the surface directed at the human realm," he says. "We can make a longer-term impact there, but it still applies back to my veterinary clinic and helps my patients. And I'm glad about that."