Complement Inhibitor Reverses Periodontitis Interview with:

George Hajishengallis, D.D.S., Ph.D., Thomas W. Evans Centennial Professor University of Pennsylvania Penn Dental Medicine - Microbiology Philadelphia, PA 19104-6030

Dr. George Hajishengallis

George Hajishengallis, D.D.S., Ph.D.,
Thomas W. Evans Centennial Professor
University of Pennsylvania
Penn Dental Medicine – Microbiology
Philadelphia, PA 19104-6030 What is the background for this study? What are the main findings?

Dr. Hajishengallis: The current study is the result of eight years of collaboration with my colleague at Penn Medicine, Dr. John D. Lambris. In our earlier mechanistic studies, we have shown that complement, a system of innate immunity and inflammation, is critically involved in the pathogenesis of periodontitis, an oral inflammatory disease that leads to the destruction of the tissues (gums and bone) that support the teeth. C3 is the central component of the complement system, where all activation pathways converge. Therefore, we reasoned that blocking C3 with an appropriate inhibitor could block the development of periodontitis. The results of this study confirmed our hypothesis. Indeed, by administering the C3 inhibitor Cp40 to the periodontal tissue just once a week reversed naturally occurring chronic periodontitis in a preclinical model. Specifically, Cp40 inhibited pre-existing gingival inflammation (as determined by both clinical and laboratory assessment) and the formation of osteoclasts, that is, the cells involved in the resorption of bone. If you are suffering from something like periodontitis, then you might want to consider getting treatment for it. For more information on what this type of treatment could be, you can always research osseous surgery. What should clinicians and patients take away from your report?

Dr. Hajishengallis: Although in this study Cp40 was successfully applied as a stand-alone treatment, it can be envisioned as an adjunctive therapy to the management of human chronic periodontitis. Cp40 has now been developed for human clinical applications (AMY-101; Amyndas Pharmaceuticals). Future clinical trials could investigate the potential of Cp40/AMY-101 to inhibit periodontal inflammation and bone loss compared to scaling and root planing, whereas in very severe cases of the disease, the drug could be combined with scaling and root planing and compared to periodontal surgery, in an effort to obviate the need for a surgical approach. What recommendations do you have for future research as a result of this study?

Dr. Hajishengallis: There are different candidate approaches for the treatment of periodontitis. Our current work shows that strategies that aim to control the host inflammatory response have a great therapeutic potential. Future research should focus on translating important findings from preclinical models to the clinic. Dissecting mechanisms of disease is very important but translating this type of research into new and effective therapies is even more significant. Is there anything else you would like to add?

Dr. Hajishengallis: As I alluded to earlier, Cp40/AMY-101 has a great potential to find application as a novel anti-inflammatory treatment for periodontitis. Periodontitis has a serious public health impact and economic burden, therefore, we need innovative treatments adjunctive to existing therapies – such as mechanical removal of the tooth-associated biofilm – which are not always sufficient to control periodontitis. This drug would not necessarily be implemented in a therapeutic setting (as used in our study) but could also be provided on a preventive basis to high-risk individuals for periodontitis, such as cigarette smokers and diabetic patients. Since Cp40/AMY-101 is intended for local treatment of human periodontitis,potential safety considerations are unlikely to apply, although of course this will need to be verified. It should be noted though that no adverse effects were observed in the preclinical studies. Thank you for your contribution to the community.


J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.

Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Maekawa T1,2, Briones RA3, Resuello RR4, Tuplano JV4, Hajishengallis E5, Kajikawa T1, Koutsogiannaki S6, Garcia CA3, Ricklin D6, Lambris JD6,Hajishengallis G1.

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Last Updated on March 31, 2016 by Marie Benz MD FAAD