Dental Tribune India

New experimental drug promises hope for those with diabetic periodontal disease

By DT SEA, Niranjan Prabhakar
September 02, 2017

An experimental drug that mimics an insulin-regulating hormone could rebuild bone, and perhaps advance treatment for Type 2 diabetics.

Almost half of adults over age 30 in the United States have periodontal disease. In most cases, a few visits to the dentist take care of the problem. In patients with Type 2 diabetes, however, gum disease is extremely difficult to treat, because systemic inflammation can cause it to spread unchecked, leading to tooth loss and massive erosion of jawbone.

“Diabetic patients have a much higher chance of developing Periodontitis than the rest of the population, and when they do get it, it’s very difficult to handle,” said Jake Jinkun Chen, a professor and molecular biologist at Tufts School of Dental Medicine whose lab studies diabetes-associated periodontal disease. The lab is exploring a promising new way to treat resistant cases with an experimental drug that mimics the behavior of the hormone adiponectin in the body; adiponectin helps regulate glucose levels as well as the breakdown of fatty acids.

Produced by fat cells, adiponectin can signal the body to generate more bone in areas where it has been lost. Bone is actually a moving organ in the body, Chen said. It’s constantly being produced and broken down by two families of cells: osteoblasts, which create new bone, and osteoclasts, which resorb it. “In healthy bone, osteoblasts and osteoclasts are constantly working together. There’s a balance of bone resorption and bone formation,” he said. “In periodontal disease, though, that balance is thrown off. There’s excess resorption and bone loss.”

When adiponectin is released into the bloodstream, it tells osteoclast cells to slow down and stop reproducing. At the same time, it coaxes osteoblasts—the body’s bone makers—into creating hard, calcifying structures along diseased bone sites, essentially healing those areas.

Although adiponectin helps the body reverse bone loss, using it to treat periodontal disease isn’t ideal, because it would have to be continuously administered through an IV. Even more important, Chen said, is that adiponectin is a protein, and like any foreign body, can cause an intense immune reaction in some patients.

To get around these problems, Chen is working with the experimental compound AdipoRon, developed in Japan in 2013 as a potential oral drug for diabetes because it replicates the effects of the glucose-regulating adiponectin. Studies in mice suggest that it doesn’t pose a threat to the body’s immune system.

At the moment, however, relatively few studies explain exactly how AdipoRon works on a cellular and molecular level, and it’s still unclear what dose might help patients with persistent periodontal disease.

Chen and his research team hope to learn more in a new study in which they will disable a gene in mice that naturally creates adiponectin; this genetic knockout will help the researchers evaluate how that might affect bone density. Then they’ll administer specific doses of AdipoRon to the mice. If the drug triggers bone growth in the rodents that have lost their natural ability to make adiponectin, Chen said, it potentially could do the same thing in patients with Type 2 diabetes.

People with Type 2 diabetes, formerly called adult-onset diabetes, are able to produce some insulin, but not enough for the body to control blood sugar levels properly, or their sensitivity to insulin is low. These patients often suffer from chronic inflammation, a condition that has been linked to a host of diseases and conditions, including cancer, insulin resistance and diabetes and atherosclerotic disease.
Although Chen’s immediate focus is on diabetic Periodontitis, he hopes he’ll be able to explore other uses for the drug in the future. The National Institutes of Health in December awarded him a $2 million grant to fund his research over the next five years.

Because AdipoRon appears to have a powerful effect on bone regeneration, Chen theorizes that the drug might be able to coax bone into fusing with dental implants. It might also be used to treat
osteoporosis and bone fractures, both of which are serious concerns in diabetic patients. Compared to the general population, Chen said, diabetics have a 64-percent higher chance of fractures that resist healing, leading to a painful and prolonged recovery.

“It’s a cascade,” he said. “When you have a systemic disease, it can cause other conditions as a result.”

Reprinted with permission, Tufts Dental Medicine magazine, ©2017 Tufts University.

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