The Forsyth Institute Receives $20.7 Million for Research Trifecta

The Forsyth Institute Receives $20.7 Million for Research Trifecta
Grants to Study Periodontal Disease Progression

CAMBRIDGE, Mass., October 18, 2010??  The Forsyth Institute, the world¹s leading independent, oral health research organization, has received $20.7 million to fight periodontal (gum) disease. Three related projects will study periodontal disease progression from microbiological, genetic, host immune response and clinical perspectives. This research, funded by the National Institute of Dental and Craniofacial Research (NIDCR), will take place over a four-year period. The ultimate goal is to gain an understanding of why people develop gum disease, how the disease progresses, how to predict active disease before it occurs, and ultimately, how therapies can be developed to improve periodontal and overall health.

Forty percent of adults in the United States have some form of periodontal disease. It is one of the most common infectious diseases and in its more severe forms causes loss of the bone that supports the teeth. In addition, there are strong associations between periodontal disease and systemic diseases including diabetes, metabolic syndrome, cardiovascular disease, pre-term birth, and certain cancers.

Previous work at Forsyth has demonstrated that the progression of the disease is not continuous, but is episodic.  Thus, to understand its pathogenesis, patients must be studied to identify sites in the mouth that are undergoing active disease progression, which is the focus of these studies.  The Forsyth projects, respectively led by Dr. Ricardo Teles, Director of the Center for Clinical and Translational Research; Dr. Bruce Paster, Head, Department of Molecular Genetics; and Dr. Jorge Frias-Lopez, Assistant Member of Staff, Department of Molecular Genetics, will examine clinical parameters, expression of host derived molecules, bacterial ecology, and bacterial gene expression during active disease.  It will also seek to identify biomarkers in blood, saliva, and gingival crevicular fluid (a fluid that oozes from the gum margin) samples from 500 individuals, both with and without existing gum disease. The data gathered by Forsyth¹s scientists as well as aliquots of the samples will be made available to the scientific community and will represent the largest available information base and depository of samples for periodontal disease.

³The knowledge developed through these three linked projects will provide unique and extraordinarily valuable insights into the periodontal disease process, as well as serve as a one of a kind resource to the scientific community,² said Philip Stashenko, President and CEO of The Forsyth Institute. ³This work represents the multidisciplinary epitome of periodontal disease research. We may be able to finally lay a firm foundation to understand why periodontal disease progresses. It is extremely rare for three projects to receive awards linked to one clinical trial, and this support from NIDCR is a testament to the promise of this research.²

The three projects were funded due to the strength of each projects and the overall potential impact of the collaborative research. The Forsyth team will also work with four other oral health research centers around the country. The Michigan Center for Oral Health Research is the first clinical research partner. Four additional research facilities will join the project shortly.

Project Overviews
Biomarkers of Periodontal Disease Progression This project, led by Dr. Ricardo Teles, received a grant of $12.7 million over four years.  In his work, Dr. Teles will study microbial and host-derived biomarkers to determine if someone is likely to develop gum disease or if existing disease is likely to worsen. The long term goal of Dr. Teles¹ research is to develop a point-of-care (POC) diagnostic test to help clinicians identify sites and/or subjects that are susceptible to periodontal disease progression. Currently, there are no rapid tests for identifying these worsening periodontal sites and subjects in a clinical setting.  Better biomarkers of periodontal disease activity are urgently needed to improve periodontal disease diagnosis, guide therapy, monitor activity and evaluate treatment response.

Oral Microbial Biomarkers in Periodontal Disease Progression Dr. Bruce Paster and his team will examine gum disease from a microbial perspective. This project, which received an award of $4 million over four years, will look at oral microbial profiles every two months to see what bacteria are present when gum disease progresses. The long-term goal of the proposed research is to be able to diagnose and predict periodontal disease before there are clinical symptoms of the disease.  This project will employ a recently developed human oral microbial identification microarray, termed HOMIM, developed by Dr. Paster and his colleagues, that can simultaneously identify 325 of the most prevalent oral bacteria, including many that cannot yet be grown in the laboratory. Although it is known that there are marked differences in the microbial composition of plaque from healthy sites as compared to those sites with periodontal disease, the microbial profiles of healthy sites that progress to active disease are yet unknown.  Ultimately, the outcome of this research has great promise for bench-to-chairside applications where clinicians will be able to determine and treat those periodontal sites at risk for disease on the basis of microbial composition.

Metatranscriptome of the Oral Microbiome during Periodontal Disease Progression This project, headed by Dr. Frias-Lopez, received funding of $4 million over four years. The goal of this study is to identify in situ the molecular mechanisms of bacterial pathogenesis by which periodontitis progresses in some sites while in others the disease remains latent. Metagenomic and metatranscriptomic analysis (gene expression analysis of entire complex bacterial communities in situ) provides the information required to understand the activity and relative importance of the tens of thousands of genes that are expressed in the pathogenic biofilm during periodontal progression.  Identification of critical genes that are required for pathogenesis and information about their differential expression can be used to develop novel targeted approaches to early-stage diagnosis, treatment, monitoring and prevention. Moreover, the potential impact extends beyond the study of periodontitis because the same principles and methods can potentially be applied to other polymicrobial diseases.