Complement Inhibitor Reverses Periodontitis

MedicalResearch.com 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

MedicalResearch.com: 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.

MedicalResearch.com: 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.

MedicalResearch.com: 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.

MedicalResearch.com: 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.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

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.

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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George Hajishengallis, D.D.S., Ph.D. (0). Complement Inhibitor Reverses Periodontitis MedicalResearch.com

Bacteria P. gingivalis Could Be Risk Factor for Esophageal Cancer

MedicalResearch.com Interview with:

Dr. Huizhi Wang Assistant Professor Department of Oral Immunology and Infectious Diseases University of Louisville School of Dentistry Louisville, KY

Dr. Huizhi Wang

Dr. Huizhi Wang
Assistant Professor
Department of Oral Immunology and Infectious Diseases
University of Louisville School of Dentistry
Louisville, KY 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Wang: Esophageal cancer is the eighth most frequent tumor and sixth leading cause of cancer death worldwide, characterized by rapid development and poor prognosis, including high mortality. Whereas the majority of cases occur in Asia, particularly in central China, recent data suggest that the frequency of new cases is rising in Western Europe and the USA. Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) was unknown before our study. We found P. gingivalis infects epithelium of cancerous tissues up to 61%, as compared with 12% of adjacent tissues and non-infected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis DNA was observed. Moreover, we found infection of P. gingivalis was positively associated with the multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate.  Continue reading

New Teeth: Why Can’t We Be More Like Sharks?

MedicalResearch.com Interview with:

Shark Teeth: lower jaw with 4 tooth rows and 4 tooth series labeled. "Series 1" contains the functional teeth at the front of the jaw. Wikipedia Image

Shark Teeth: lower jaw with 4 tooth rows and 4 tooth series labeled. “Series 1” contains the functional teeth at the front of the jaw. Wikipedia Image

Gareth J. Fraser, Ph.D
Lecturer in Zoology
Department of Animal and Plant Sciences
Alfred Denny Building
University of Sheffield
Western Bank Sheffield UK

MedicalResearch: What is the background for this study? What are the main findings?

 

 

Dr. Fraser: Our study shows how sharks develop their formidable, continuously regenerative conveyor belt-like dentition. We show how sharks make and regenerate their teeth utilising a core set of highly conserved genes shared among all vertebrates, including humans. This network of genes has been making teeth in vertebrates for over 400 million years. This report suggests that all teeth are made with this same group of genes. Sharks have an incredible ability to rapidly regenerate their dentition throughout life, and these genes are essential for this process of regeneration.

If we compare this process to mammals where the regenerative system is greatly reduced with only two sets of teeth, then we can begin to understand why humans have lost the ability to regenerate their dentition more than once. The beauty of studying natural systems like the shark dentition is that we can learn the basic science behind how teeth are naturally regenerated. This is important to human dental health as we can use these natural systems of tooth regeneration to learn about the essential cells and genes that regulate the process of natural tooth regeneration.

In the future, this research could facilitate the development of new dental therapies helping humans to regrow natural teeth when required.

Citation:

Liam J. Rasch, Kyle J. Martin, Rory L. Cooper, Brian D. Metscher, Charlie J. Underwood, Gareth J. Fraser. An ancient dental gene set governs development and continuous regeneration of teeth in sharks.
Developmental Biology, 2016; DOI:10.1016/j.ydbio.2016.01.038

Dr. Gareth Fraser (2016). New Teeth: Why Can’t We Be More Like Sharks? 

Periodontal Disease Linked to Breast Cancer Risk in Postmenopausal Women

Jo Freudenheim, PhD UB Distinguished Professor and Interim Chair Department of Epidemiology and Environmental Health School of Public Health and Health Professions University at Buffalo Buffalo, NY

Dr. Jo Freudenheim

MedicalResearch.com Interview with:
Jo Freudenheim, PhD
UB Distinguished Professor and Interim Chair
Department of Epidemiology and Environmental Health
School of Public Health and Health Professions
University at Buffalo
Buffalo, NY

Medical Research: What is the background for this study? What are the main findings?

Dr. Freudenheim: There have been a number of studies that have shown an association between periodontal disease and chronic diseases, particularly stroke and heart attacks. There is also some newer evidence that periodontal disease is associated with cancer, particularly cancers of the gastrointestinal tract. Ours is the first large prospective study of periodontal disease and breast cancer.

This was part of a study of more than 70,000 postmenopausal women from throughout the United States, the Women’s Health Initiative. Women provided information about their health and other related factors and then those women were followed to see who developed certain diseases.

We found that women who had been told that they had periodontal disease were more likely to develop breast cancer. In particular, women who were former smokers (quit within the last 20 years) and who had periodontal disease were at increased breast cancer risk. There was a similar increase in risk for current smokers with periodontal disease but it was not statistically significant. (There was a relatively small number of current smokers in the WHI study.)

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Secondhand Smoke Exposure Doubles Risk of Cavities in Children

Dental Cavity Wikipedia

Dental Cavity
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MedicalResearch.com Interview with:
Koji Kawakami, MD, PhD
Professor and Chair, Department of Pharmacoepidemiology and Clinical Research Management
Graduate School of Medicine and Public Health
Director, Science for Innovation Policy Unit, Center for Promotion of Interdisciplinary Education and Research
Kyoto University Kyoto city
Kyoto Japan

Medical Research: What is the background for this study? What are the main findings?

Dr. Kawakami: The prevalence of caries in deciduous teeth in developed countries remains high, while established measures for caries prevention in young children is limited to sugar restriction, oral fluoride supplementation and fluoride varnish. In this study of 76920 children in Japan, exposure to tobacco smoke at 4 months of age, which was experienced by half of all children of that age, was associated with an increased risk of caries in deciduous teeth by approximately 2-fold.

Medical Research: What should clinicians and patients take away from your report?

Dr. Kawakami: Our findings would support extending public health and clinical interventions to reduce secondhand smoke. For example, the chance of education on the harm of secondhand smoke would increase if dentists become aware of the caries risk due to secondhand smoke as well as tobacco smoking of their patients.

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Despite Claims, Xylitol May Not Help Prevent Tooth Decay

Xylitol Wikipedia

Xylitol
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MedicalResearch.com Interview with:
Philip Riley
Cochrane Oral Health Group, School of Dentistry
The University of Manchester
Manchester, UK

Medical Research: What is the background for this study? What are the main findings?

Response: As tooth decay is still so prevalent worldwide, despite being entirely preventable, it is worth assessing the evidence for other adjunctive ways for the public to help prevent the disease. Manufacturers of xylitol products commonly make the claim that this natural sweetener prevents tooth decay, and we felt that the public deserved to know if the best quality evidence backs up such claims.

We found that there was a lack of evidence from randomised controlled trials (the best type of study design for testing the effects of interventions) to prove that xylitol products can prevent tooth decay. We found some low quality evidence suggesting that xylitol added to fluoride toothpaste may reduce tooth decay in children’s permanent teeth by 13% over a 3 year period when compared to fluoride toothpaste without xylitol. However, these findings should be interpreted with caution and may or may not be generalizable to other populations. There was insufficient evidence to conclude that xylitol in chewing gums, lozenges, candies/sweets, syrups and wipes can prevent tooth decay in children or adults

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Periodontitis Linked To Larger Myocardial Infarct Size

Dr. Francisco Mesa Department of Periodontics, School of Dentistry, University of Granada, Spain

MedicalResearch.com Interview with:
Dr. Francisco Mesa
Department of Periodontics,
School of Dentistry, University of Granada, Spain



Medical Research: What is the background for this study? What are the main findings?

Dr. Mesa: The size of an acute myocardial infarct (AMI) is one of the determinants of its severity, i.e., the degree of myocardial necrosis. This necrosis is indicated by peak troponin I levels in the blood. Among the acute myocardial infarct patients in our study, mediated regression analysis demonstrated that troponin I levels were higher, i.e., the infarct size was larger, in those with chronic periodontitis.

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