When the population of bacteria in our mouths gets out of whack, inflammation and bone loss can ensue—a disease of the gums called periodontitis. Nearly half of American adults have this condition, which, when severe, can lead to systemic illnesses like heart disease and diabetes.

A collaboration among researchers from the School of Dental Medicine and the Perelman School of Medicine may hold out some hope for a promising treatment, resulting in a new target for preventing and possibly reversing periodontitis: a molecule that makes up a part of our own immune arsenals called complement.

The Penn team was led by George Hajishengalli, a professor in Penn Dental’s Department of Microbiology, and John Lambris, the Dr. Ralph and Sallie Weaver Professor Research Medicine in Penn Medicine’s Department of Pathology and Laboratory Medicine.

“Our work demonstrates a proof-of-concept that complement-targeted therapies can interfere with disease-promoting mechanisms,” Hajishengalli says.

The researchers knew from earlier studies that Porphyromonas gingivalis—the bacterium responsible for many cases of periodontitis—plays a game of subterfuge in the body. It has various strategies that prevent it from being killed by the immune system, yet it paradoxically feeds off the inflammation that the immune response creates. To ensure it can survive and thrive, P. gingivalis has evolved mechanisms that help it suppress the immune system so that other bacteria in the mouth can flourish and further inflame the gums.

To determine what element of the immune system was involved in contributing to this inflammation, the researchers investigated the complement system—part of the innate immune system that acts as a primary responder to invading microbes and is central in triggering an inflammatory response.

Experiments in mice showed that a complement molecule called C3 was critical for sustaining P. gingivalis infection over the long term. As it happens, a drug that inhibits C3, called Cp40, was already in development to treat other diseases. Mice don’t respond to Cp40, but monkeys do. By administering Cp40 to the gums of monkeys, the researchers were able to reduce inflammation and significantly prevent bone loss—signs that the drug was effectively protecting the animals against periodontitis.

“We think this drug offers a promising possibility for treating adults with periodontitis,” Lambris says. “Blocking C3 locally in the mouth helps shift the balance of bacteria, producing an overall beneficial effect.”