A compound discovered by Novartis researchers prompts regeneration of cartilage in mice — and may pave way for the development of treatments to reverse painful osteoarthritis.
About 27 million Americans with osteoarthritis know with painful clarity that — unlike the cells of the skin, liver and stomach — the cells of the cartilage don’t regenerate. When the cartilage — that supple, slippery tissue covering joints — wears down, bones rub against each other, causing much pain and disability.
Currently, the only treatments for arthritis are anti-inflammatory and surgery and in severe cases, the joints are replaced. There’s still no way to reverse the disease, even as it affects most elderly people — it affects half of all 50-year-olds, 60 percent of 60-year-olds and an increasing proportion of people as they grow older.
Each year, surgeons in the United States carry out more than 600,000 total knee replacements and 285,000 hip replacements because of arthritis and other injuries. In the United Kingdom, the National Health Service performs out more than 140,000 hip and knee replacements each year.
But all measures show limited success. Anti-inflammatory painkillers can damage the stomach when used for a long time. Artificial hips or knees can wear out after 15 years, and many patients have to undergo another operation.
Arthritis patients can also opt to undergo surgery to clean out torn cartilage or surgery to induce growth of a fibrous kind of coating at the ends of bones that have lost their natural cartilage caps — but both procedures result in limited success — leaving patients with a losing battle against bone-on-bone friction, inflammation and pain.
The ailment also burdens the health care system with extra costs — an extra US$185.5 billion annually, according to a 2009 study by researchers from the New York’s Stony Brook University, cited by U.S. health and science reporter Bradley J. Fikes. In the U.K., arthritis procedures cost taxpayers more than 1 billion pounds a year.
What about regenerating cartilage, instead?
It’s no wonder then that regenerating the cartilage-making process in the body has become a primary goal in orthopedic medicine.
Now, scientists at Novartis AG (NOVN) have leapt much closer to that goal by discovering a compound called kartogenin that encourages stem cells to grow cartilage, fixing damaged joints of arthritic lab mice.
The Novartis investigators found that when they injected kartogenin into the damaged joints of mice with osteoarthritis-like symptoms, the compound prompted cartilage to regenerate, and the mice regained their ability to use the joint without pain. They also found lowered levels of proteins and collagen fragments linked to damaged joints.
Researchers started out by using mesenchymal stem cells — which reside naturally in cartilage and give rise to chondrocytes, the cells in the body that make cartilage.
Then they went on to search for a chemical that could act as a trigger, transforming stem cells into cartilage, safely and effectively, without requiring implants.
To discover kartogenin, the investigators painstakingly tested 22,000 drug-like molecules using a robotic screen — they applied each of the molecules to bone marrow stem cells in Petri dishes. Unlike the other molecules, Kartogenin appeared to “wake” the stem cells, spurring them to begin making cartilage.
The researchers also conducted tissue studies with cultures of bovine cartilage and found evidence that kartogenin also protects cartilage from damage.
While these are early findings, they provide new clues to solving the long-running puzzle of how to regenerate cartilage — and thus suggest a novel way to repair some of the damage from osteoarthritis, the researchers claim. Their findings are published online in the April 5 issue of the journal Science.
“In mice, we were able to see that there is significant repair,” says study co-author Kristen Johnson, a molecular biologist at the Genomics Institute of the Novartis Research Foundation in San Diego, California. “You can tell there is a difference,” she says.