Periodontal paradigm shift
By Tim Stoddard
The grisly images are enough to make you floss daily. On the wall in every dental office, cautionary posters show the consequences of poor oral hygiene: red, puffy gums that bleed easily, crumbling teeth, and festering sores that destroy ligament and bone. For Thomas Van Dyke, a professor of periodontology and oral biology at the Goldman School of Dental Medicine, these graphic images tell only part of the story of gum disease.
He believes it’s time for researchers to change the way they think about the problem. As the clinical director of the new Specialized Center for Research in Oral Inflammation and Resolution, a collaboration between SDM and Harvard researchers at Brigham and Women’s Hospital, he is pursuing the radical new idea that periodontal disease is caused by too much of a good thing — in this case, inflammation, which is the body’s first line of defense against invading microbes.
Until recently, researchers thought they understood how gingivitis, an inflammation of the gums along the teeth, becomes the more serious periodontitis, where gum tissue gradually separates from the tooth, forming pockets in which bacteria thrive and burrow deeper into bone. According to the old theory, the main problem in periodontal disease is inflammation. When bacteria infect gums a battle ensues: immune cells rush in to attack invading microbes and in the process cause collateral damage to the gum tissue itself. The best way to stop inflammation is to kill the bacteria with a combination of surgery and antibiotics.
But last year Van Dyke and other SDM researchers reported that some initial inflammation is actually beneficial, and damage occurs only when the inflammatory response fails to shut off. “Periodontitis is not well understood,” he says. “We know it’s an infectious disease — it’s caused by bacteria — but it does not act like other infectious diseases, because you can’t treat it well with antibiotics. It’s starting to look like periodontal disease is more like arthritis and other inflammatory diseases than classic infectious diseases. We think that susceptibility to periodontal disease is based upon your genetically programmed inflammatory response.”
That idea is gaining ground in the field. And Van Dyke’s research team at the new center, which was created with an $8.5 million grant from the National Institute of Dental and Craniofacial Research, is at the forefront of research involving the molecular mechanisms of inflammation.
The team has already identified a promising class of molecules, called lipoxins, that appear to turn off inflammation. Rabbits that were genetically engineered to overproduce lipoxins had very little inflammation when they were exposed to bacterial infection and were resistant to periodontitis. Future studies at the center will explore how lipoxins signal the body to call off the inflammatory attack.
The ultimate goal in this research, Van Dyke says, is to translate the basic research on inflammation into pharmaceutical products. “We’re looking to eventually turn these discoveries into therapies that can be used clinically to combat inflammation,” he says.
Most periodontists treat gum disease with antibiotics, but Van Dyke says this approach has limited effectiveness. Ideally, a product containing lipoxin molecules would turn off the inflammation, thus allowing oral tissues to heal. “The problem is that these molecules are very fragile in their natural state,” he says, “so part of our efforts will involve modifying them to make them longer-acting.”
A better treatment for periodontitis would have a huge impact in the United States, where more than half of adults over age 50 have the disease. “Inflammation is the major characteristic of the disease,” Van Dyke says. “Heart disease and the complications of diabetes are inflammatory diseases, and so our research potentially has broader applicability outside of dentistry.”