Team identifies promising new target for gum disease treatment

May 20, 2014 by Katherine Unger Baillie, University of Pennsylvania

Team identifies promising new target for gum disease treatment
Complement, a key part of the innate immune system, contributes to gum disease and blocking it can prevent disease.
(Medical Xpress)—Nearly half of all adults in the United States suffer from the gum disease periodontitis, and 8.5 percent have a severe form that can raise the risk of heart disease, diabetes, arthritis and pregnancy complications.

University of Pennsylvania researchers have been searching for ways to prevent, half and reverse . In a report published in the Journal of Immunology, they describe a promising new target: a component of the called complement. Treating monkeys with a complement inhibitor successfully prevented the inflammation and bone loss that is associated with periodontitis, making this a promising drug for treating humans with the disease.

George Hajishengallis, a professor in the School of Dental Medicine's Department of Microbiology, was the senior author on the paper, collaborating with co-senior author John Lambris, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine. Their collaborators included Tomoki Maekawa, Toshiharu Abe, Evlambia Hajishengallis and Kavita B. Hosur of Penn Dental Medicine and Robert A. DeAngelis and Daniel Ricklin of Penn Medicine.

Earlier work by the Penn team had shown that the periodontal bacterium Porphyromonas gingivalis can hamper the ability of immune cells to clear infection, allowing P. gingivalis and other bacteria to flourish and inflame the gum tissue.

"P. gingivalis has many mechanisms to escape killing by the immune system, but getting rid of inflammation altogether is not good for them because they 'feed' off of it," Hajishengallis said. "So P. gingivalis helps suppress the immune system in a way that creates a hospitable environment for the other bacteria."

The researchers wanted to find out which component of the complement system might be involved in contributing to and maintaining inflammation in the disease. Their experiments focused on the third component of complement, C3, which occupies a central position in signaling cascades that trigger inflammation and activation of the innate immune system.

The team found that mice bred to lack C3 had much less bone loss and inflammation in their gums several weeks after being infected with P. gingivalis compared to normal mice. C3-deficient mice were also protected from periodontitis in two additional models of disease: one in which a silk thread is tied around a tooth, promoting the build-up of microbes, and one in which the disease occurs naturally in aging mice, mimicking how the disease crops up in aging humans.

"Without the involvement of a different complement component, the C5a receptor, P. gingivalis can't colonize the gums," Hajishengallis said. "But without C3, the disease can't be sustained over the long term."

Building on this finding, the researchers tested a human drug that blocks C3 to see if they could reduce the signs of periodontal disease in monkeys, which, unlike mice, are responsive to the human drug. They found that the C3 inhibitor, a drug called Cp40 that was development for the treatment of the rare blood disease PNH and ABO-incompatible kidney transplantation, reduced and significantly protected the monkeys from bone loss.

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

According to the researchers, this study represents the first time, to their knowledge, that anyone has demonstrated the involvement of complement in inflammatory in non-human primates, setting the stage for translation to human treatments.

The results, Hajishengallis said, "provide proof-of-concept that complement-targeted therapies can interfere with disease-promoting mechanisms."

Explore further: Research suggests a new strategy to prevent or halt periodontal disease

More information: Paper: dx.doi.org/10.4049/jimmunol.1400569

Related Stories

Research suggests a new strategy to prevent or halt periodontal disease

December 7, 2012
Periodontitis, a form of chronic gum disease that affects nearly half of the U.S. adult population, results when the bacterial community in the mouth becomes unbalanced, leading to inflammation and eventually bone loss. In ...

Researchers reverse bone loss in immune disorder

March 26, 2014
Patients with leukocyte adhesion deficiency, or LAD, suffer from frequent bacterial infections, including the severe gum disease known as periodontitis. These patients often lose their teeth early in life.

Protein plays key role in infection by oral pathogen

March 24, 2014
Scientists at Forsyth, along with a colleague from Northwestern University, have discovered that the protein, Transgultaminase 2 (TG2), is a key component in the process of gum disease. TG2 is widely distributed inside and ...

Study suggests affordable and effective treatment of rare blood disorder

February 27, 2014
A University of Pennsylvania research team has defined a possible new way to fight a disease that is currently treatable only with the most expensive drug available for sale in the United States. In a study published this ...

Drug may guard against periodontitis, and related chronic diseases

November 8, 2013
A drug currently used to treat intestinal worms could protect people from periodontitis, an advanced gum disease, which untreated can erode the structures—including bone—that hold the teeth in the jaw. The research was ...

New discovery related to gum disease

September 11, 2012
A University of Louisville scientist has found a way to prevent inflammation and bone loss surrounding the teeth by blocking a natural signaling pathway of the enzyme GSK3b, which plays an important role in directing the ...

Recommended for you

Study examines disruption of circadian rhythm as risk factor for diseases

December 11, 2018
USC scientists report that a novel time-keeping mechanism within liver cells that helps sustain key organ tasks can contribute to diseases when its natural rhythm is disrupted.

New light-based technology reveals how cells communicate in human disease

December 11, 2018
Scientists at the University of York have developed a new technique that uses light to understand how cells communicate in human disease.

Researchers explore new way of killing malaria in the liver

December 8, 2018
In the ongoing hunt for more effective weapons against malaria, international researchers said Thursday they are exploring a pathway that has until now been little studied—killing parasites in the liver, before the illness ...

Study may offer doctors a more effective way to treat neuroblastoma

December 7, 2018
A very large team of researchers, mostly from multiple institutions across Germany, has found what might be a better way to treat patients with neuroblastoma, a type of cancer. In their paper published in the journal Science, ...

Progress made in transplanting pig hearts into baboons

December 6, 2018
A large team of researchers from several institutions in Germany, Sweden, Switzerland and the U.S. has transplanted pig hearts into baboons and kept them alive for an extended period of time. In their paper published in the ...

'Chemo brain' caused by malfunction in three types of brain cells, study finds

December 6, 2018
More than half of cancer survivors suffer from cognitive impairment from chemotherapy that lingers for months or years after the cancer is gone. In a new study explaining the cellular mechanisms behind this condition, scientists ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.