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Researchers Reverse Signs of Naturally Occurring Chronic Periodontitis

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    Periodontitis, a gum disease present in nearly half of all adults in the United States, involves inflammation, bleeding and bone loss. In its severe form, it is associated with systemic inflammatory conditions such as atherosclerosis and rheumatoid arthritis. Few treatment options exist beyond dental scaling and root planning, done in an attempt to reduce plaque and inflammation.

    University of Pennsylvania scientists described research whose results might eventually lead to the reversal of the severe gum disease periodontitis.

    The study (“Inhibition of Pre-Existing Natural Periodontitis in Non-Human Primates by a Locally Administered Peptide Inhibitor of Complement C3″), which appears in the Journal of Clinical Periodontology, employed an inhibitor of the C3 protein, a component of the body’s complement system that is involved in immunity and inflammatory responses. Delivering this inhibitor, Cp40, to the periodontal tissue once a week reversed naturally occurring chronic periodontitis inflammation in a preclinical model.

    George Hajishengallis, D.D.S., Ph.D., Thomas W. Evans Centennial Professor in Penn’s School of Dental Medicine’s Department of Biology, and John D. Lambris, Ph.D., Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Perelman School of Medicine’s Department of Pathology and Laboratory Medicine, were co-senior authors on the study.

    “Even after one treatment, you could see a big difference in inflammation,” said Dr. Hajishengallis. “After six weeks, we saw reversals in inflammation, both clinically and by looking at cellular and molecular measures of osteoclast formation and inflammatory cytokines.”

    “The results were so clean, so impressive,” added Dr. Lambris. “The next step is to pursue Phase I trials in humans.”

    This study builds on earlier work by the team, which identified C3 as a promising target for treating periodontal disease. C3, or the third component of the complement system, is a key part of signaling cascades that trigger inflammation and activate the innate immune system. Their previous research, which used an inducible model of periodontal disease, found that Cp40 could reduce signs of the disease.

    To get closer to a natural scenario, however, the current work was conducted on animals that had developed chronic periodontitis naturally. Initially the research team tried administering Cp40 three times a week, but after seeing significant reductions in inflammation, they tried giving it only once a week to a different group and saw the same good results.

    “Statistically, giving the drug only once a week was indistinguishable from three times a week,” noted Dr. Hajishengallis.

    This study delivered the drug via a local injection to avoid any potential systemic effects from inhibiting a component of the immune system. There were no adverse effects reported.

    “Some people have been concerned that blocking complement would lead to more infections but that is not the case here,” according to Dr. Lambris. “We’re stopping the inflammation in the gums and thereby killing the bacteria that need inflammatory tissue breakdown proteins to survive.”

    The researchers are even more encouraged that this treatment worked well as a stand-alone therapy; in humans, they said, it would be given in addition to the standard of care scaling and planing. They are planning to pursue a Phase I safety and efficacy study in human volunteers.

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