Reversal of Periodontitis Achieved via Inhibition of C3

Researchers have developed a means of reversing periodontitis, inflammation of the gums, in an animal model. This is of interest in the context of aging as periodontitis is widespread in the population, and inflammation in the gums doesn't remain isolated: it spreads to contribute to the progression of much more dangerous conditions such as atherosclerosis. A clinical therapy that eliminates periodontitis entirely would be a very positive advance.

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 planing, done in an attempt to reduce plaque and inflammation. Now, however, researchers have employed an inhibitor of a protein called C3, a component of the body's complement system, which is involved in immunity and inflammatory responses. Delivering this inhibitor, Cp40, to the periodontal tissue just once a week reversed naturally occurring chronic periodontitis inflammation in a preclinical model. "Even after one treatment, you could see a big difference in inflammation. 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. The next step is to pursue Phase 1 trials in humans."

This study builds on earlier work 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 naturally had developed chronic periodontitis. 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. 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. We're stopping the inflammation in the gums and thereby killing the bacteria that need inflammatory tissue breakdown proteins to survive."

Link: https://news.upenn.edu/news/penn-team-reverses-signs-naturally-occurring-chronic-periodontitis

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