From rxpgnews.com

Dental
Study will provide basis for targeted therapies for leading cause of adult tooth loss
Sep 10, 2004 - 3:15:38 PM

Scientists at Columbia University Medical Center (CUMC) are looking into the genetic reasons why individuals experience periodontal disease so differently, and why some respond to treatment more successfully than others. Even with treatment, some patients continue to see deterioration of gum condition and eventual loss of teeth.

The research is part of an effort at CUMC to eradicate periodontitis in these patients and better understand how the gum disease develops, and will allow the development of pharmacologic therapies targeted specifically to a person's own genetic predisposition for response.

A new three-year, $1.8 million grant from the National Institute of Dental & Craniofacial Research will support research to determine whether different forms of periodontitis can be classified based on gene expression in inflamed gums.

Periodontitis occurs when infection of the gums goes untreated and inflammation spreads to ligaments and bone that support the teeth. The disease is the leading cause of tooth loss in adults.

Currently, periodontitis is classified into two groups – chronic and aggressive – that are categorized based on clinical signs after consideration of medical and oral health history. However, distinguishing these two disease categories can be difficult because the clinical signs of both can be quite similar, while response to standard therapeutic procedures may vary considerably. Both types of disease are characterized by swollen gums and deep periodontal pockets. Therapy usually consists of cleaning of the periodontal pockets and root surfaces, accompanied by gum surgery and adjunctive antibiotics.

"The current system for classifying periodontal disease does not have a solid, pathobiology-based foundation," said Panos N. Papapanou, D.D.S., Ph.D., the principal investigator on the project, who is also professor and chair of the Section of Oral and Diagnostic Sciences and director of the Division of Periodontics, Columbia University School of Dental & Oral Surgery. "We intend to identify the molecular basis of the wide spectrum of responses to periodontal bacteria, and use this information to reduce the risk of periodontitis and develop new, more targeted therapies."

The patient's individual immuno-inflammatory response to the bacterial challenge is believed to determine the type, extent and severity of periodontitis, and this response is believed to have a strong genetic component. Dr. Papapanou and his team will examine gene expression signatures to define different subtypes of the disease in order to understand the molecular processes involved in each subtype.

The research will take advantage of contemporary gene expression profiling technology, similar to that used to study the behavior and prognosis of certain cancers. Dr. Papapanou and his team will study 120 patients – 60 with chronic and 60 with aggressive periodontitis. Samples of inflamed gingival tissue from the patients will be analyzed to identify local patterns of gene expression in inflamed gums, and will be used to develop a novel classification scheme based on similarities in gene expression signatures.

"In addition to providing insights into the pathobiology of periodontitis, this research will provide a wealth of data on the basic host responses to infection," said Paul Pavlidis, Ph.D., co-principal investigator of the study and assistant professor in the Columbia University department of Biomedical Informatics and the Columbia Genome Center.

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