November 30, 2006
As periodontal disease worsens around a tooth, the challenge is to stop the inflammation of the gums, or gingiva, before underlying bone erodes. “Challenge” being the operative word. The reason is the tough-to-treat gram negative bacteria that colonize the periodontal lesion are studded with chain-like surface molecules called lipopolysaccharides (LPS) that incite immune cells to initiate further inflammation and ultimately a complex biochemical cascade that leads to bone erosion.
But in recent years, basic researchers have identified a promising molecular master switch within immune cells that, if blocked from activation, has the potential to reduce the inflammation and/or bone loss of advanced periodontal disease. The switch is a cytoplasmic protein called p38 mitogen activated protein kinase that controls an internal biochemical pathway which, once turned on, generates a proinflammatory response. As published online on October 13 in the Journal of Pharmacology and Experimental Therapeutics, NIDCR grantees report proof of principle success with an orally active p38 inhibitor in treating advanced periodontal disease. The drug SD-282 provided “significant protection” from LPS-induced bone loss over an eight-week period in rats with tooth sockets that are susceptible to erosion and whose gingival lesions had stimulated LPS from Aggregatibacter actinomycetemcomitans, a gram negative oral bacterium that is strongly associated with periodontal disease.