New approach to treatment of progression of osteoarthritis

The results of the study revolve around the long-held idea that machines within animal and human cells convert the sugars, fats, and proteins we eat into energy used by the millions of cells of the body. The molecule most commonly used to conserve this energy is called adenosine triphosphate, or ATP. Along with this central role in metabolism, adenosine also helps signal other cells and serves as a building block of genetic material, and so it is central in the growth of human tissue.

Previous research had shown that maintaining supplies of adenosine, known to nourish the chondrocyte cells that make cartilage, also prevented osteoarthritis in similar animal models of the disease.

In the new NYU Grossman School of Medicine-led study, researchers examined adenosine in the joints of rodents whose limbs were damaged by inflammation that resulted from traumatic injury, such as a torn ligament, or from massive weight gain that pressure placed on joints. The biological damage in these cases is similar, say researchers, to those sustained in human osteoarthritis.

Publish online in the magazine Scientific reports on August 10, the study’s rodents received eight weeks of adenosine injections, which required re-growth of cartilage tissue between 50 percent and 35 percent as measured by standard laboratory scores.

“Our latest study shows that supplementing adenosine stores by injection works well as a treatment for osteoarthritis in animal models of the disease, and with no apparent side effects,” says lead study author Carmen Corciulo, Ph.D. a postdoctoral fellow at NYU Langone.

Corciulo says it is too early to use this experimental model as a therapy in humans. Clinical trials have to wait for a test medication that can be stored safely for days or weeks, and experiments in larger mammals.

Studying senior researcher Bruce Cronstein, MD, the Dr. Paul R. Esserman, professor of medicine at NYU Langone Health, says the team’s research is important because the few existing drug therapies for osteoarthritis, such as acetaminophen and COX-2 inhibitor drugs, including naproxen and ibuprofen, only narrow joint pain, or like hyaluronic acid, simply lubricating its tissues. No one claims disease progression or reverses the damage. Painkillers, such as opioids, are often prescribed, but are also highly addictive, he warns.

“People with osteoarthritis desperately need more treatment options with fewer side effects, and our research advances this effort,” says Cronstein, who also serves as director of the Institute for Clinical and Translational Science (CTSI). He noted that other experimental drugs are being developed elsewhere, including parathyroid hormone to grow bones, WNT inhibitor drugs to block the degradation of bones and cartilage, and growth factor chemicals for cartilage growth.

Cronstein, Corciulo, and NYU Grossman School of Medicine have filed a patent application pending the use of adenosine and other agents that help with their binding to chondrocytes, called A2A receptor agonists, for the treatment of osteoarthritis.

Among the other key findings of the study was that a signaling pathway known as transformative growth factor beta (TGF-beta) and involved in many forms of tissue growth, death and differentiation, was highly active in cartilage tissue compromised by osteoarthritis, as well as in cartilage tissue that repairs after being treated with adenosine. Additional tests in lab-grown chondrocytes of people with osteoarthritis showed different chemical profiles of TGF-beta signal at onset than during growth, and provide the first evidence that the pathway inhibited function in the presence of adenosine (of assisted in degradation of cartilage to stimulate repair.)

Developing treatments to stop or slow the disease is important, says Cronstein, because well over 100 million people worldwide are suffering from osteoarthritis, which is linked to aging, especially in women. This figure, he says, is only expected to grow as more people live longer and obesity rates climb.

“Right now, the only way to stop osteoarthritis is to have the joints that have been surgically replaced, which not only comes with pain and risk of infection, but is also quite costly,” says Cronstein. “If new therapies can cure or prevent disease, then less common replacements will save people a lot of pain and expense.”