NewsletterThe Vice President for Clinical and Translational Research and Chair of the Department of Applied Oral Sciences at The Forsyth Institute discusses the impact of translational research on periodontal disease and dental practice.
Interview by David C. Alexander, BDS, MSc, DDPH
THOMAS E. VAN DYKE (TEVD): I went to dental school because I was interested in science, and dentistry seemed like a good profession. But while practicing as a general dentist in the army after graduation, I realized that I didn’t want to do that every day. Because my first interest was science and I was advised by my first mentor, Morris Matt, DDS, at Case Western Reserve University (CWRU), that I’d need a specialty, as well as a PhD, to advance professionally, I eventually completed the combined PhD: Periodontology program at State University of New York at Buffalo, New York. Among those who impacted my career were: David Scott, DDS, my dean at CWRU Dental School, who became Director of National Institute of Dental and Craniofacial Research (NIDCR); Mark Patters, DDS, PhD, a longtime friend from college and dental school who urged me to consider the Buffalo program; Robert Genco, DDS, PhD, a strong influence and source of support at Buffalo, and, of course, Michael Levine, DDS, PhD, my PhD major professor. I probably would never have survived Michael’s lab without the friendship and guidance of my lab mate, Larry Tabak, DDS, PhD, who is currently Deputy Director of National Institutes of Health. After completing the Buffalo program, I spent 9 years at Emory University in Atlanta, Georgia. After Emory’s dental school closed, I completed a short tour of duty during Desert Storm at Fort Gordon in Augusta, Georgia, before assuming a position at the Eastman Dental Center in Rochester, New York. I was recruited by Boston University in 1995, where I spent 15 years as Director of the Postgraduate Program in Periodontology and the Clinical Research Center.
TEVD: In 2010, I was appointed Vice President for Clinical and Translational Research and Chair of Applied Oral Sciences at the Forsyth Institute, which was founded in 1914 as The Forsyth Dental Infirmary for Children. After World War II, Forsyth became a preeminent dental research institute. Today, Forsyth is an independent institute that addresses research questions from basic science to clinical application. One of our success stories in public health is ForsythKids, a highly effective caries treatment and prevention program that reduced the untreated caries rates among children in inner-city schools from 80% to 20% over an 8-year period.
Since my arrival, the Institute’s research portfolio has become more diverse, with 18 clinical and translational protocols added to an already busy basic and clinical science agenda. The goal of our program is to transfer our basic laboratory discoveries through animal trials to clinical trials and into practice. Forsyth has an impressive track record performing basic research through translational research at different levels—both animal and human—to product development.
TEVD: A number of the Institute’s major past discoveries have dramatically impacted public health and dental practice. Its fluoride research contributed to widespread water fluoridation, as well as fluoride-based toothpastes, rinses, and other products. The Institute is also credited with playing a major role in the identification of the major organisms associated with caries and periodontal disease. Investigators at Forsyth now lead the oral section of the Human Microbiome Project. The role of periodontal inflammation in the pathogenesis of disease is a current area of study that suggests that while the etiology of periodontal disease is bacteria, the pathogenesis is inflammatory.
As a result of more recent research linking oral disease to so-called non-communicable, inflammatory conditions, such as diabetes and cardiovascular disease, paradigms of treatment are changing. Dentists now must consider treating the whole patient. For example, there is now an epidemic of diabetes in the United States, and patients typically see their dentists far more often than their physicians. Therefore, should dentists be considered a point of care at which patients at risk for such conditions be identified and referred to primary care physicians for follow up? The relationship of periodontitis to cardiovascular diseases is becoming equally compelling. Emerging data suggest that dental care can impact the outcome of systemic disease and general well being.
TEVD: For the last 15 years, a major focus has been the periodontal characterization of a new class of eicosanoids (lipids) discovered by Charles N. Serhan, PhD, at Brigham and Women’s Hospital in Boston. These low-molecular-weight eicosanoids of the same class as prostaglandins and leukotrienes actively resolve inflammation. This is a perfect example of translational research. New biochemical pathways were identified in the laboratory and new molecules evaluated on a cellular level. Once the potential in inflammatory disease was established, the molecules were tested in animal disease systems. It was found that they are very effective at treating—not just preventing—periodontal disease in mice and rabbits. The next step is human clinical trials, where it can be determined whether these findings may lead to a new treatment—possibly a medicinal topical compound—that will reverse inflammation and allow for regeneration of periodontal tissues.
On the basic science level, there is a program to determine the role of resolving molecules in the pathogenesis of type 2 diabetes, which is characterized by an attendant hyper-inflammatory phenotype. People with type 2 diabetes have more inflammation, and many of the complications of type 2 diabetes—including periodontitis—are attributable to that inflammation. The main question is: Does inflammatory disease result from a failure of resolution? On a more clinical dentistry pathway, we are examining the role of inflammation in tissue regeneration. The major hypothesis here is that tissues fail to regenerate—in, for example, guided tissue regeneration (GTR) in periodontics—because of inflammation. Here, the question is: If inflammation control can be achieved, possibly through the use of molecules that actively resolve inflammation, will the tissues regenerate completely? The clinical impact would, of course, be to make GTR a very predictable procedure, as opposed to current outcomes, which in many cases are hit and miss.
TEVD: The knowledge that periodontitis is an inflammatory disease has not yet significantly changed management approaches, nor has the concept gained general acceptance by the profession. Incremental efforts have been made in that direction, including the use of nutraceuticals, such as omega-3 fatty acids, in attempts to promote resolution of inflammation. I would emphasize that resolution of inflammation is very different from inhibition of inflammation with non-steroidal anti-inflammatories (NSAIDs). NSAID therapy cannot be used long term because of potentially severe side effects, and there is no known impact on regeneration. Currently, dentists must continue to attempt to control inflammation by controlling dental plaque. The hope and expectation over the next 10 years is that dentistry will benefit from the widespread use of more potent yet safe pharmacological methods to control inflammation once they become available.
Ideally, periodontal disease should be entirely preventable, but it is more likely that there will still be a population that gets the disease. However, I believe that with effective control of inflammation, periodontal disease will be vastly reduced and regenerative procedures will be more predictable. There will also be a greater effort devoted to saving existing teeth rather than turning to implants.
In short, I think the biggest change in the world of periodontics will be a movement into tooth-preserving periodontal medicine and away from implants. There will be a greater effort to treat conditions medically, and to combine surgery that is necessary with periodontal medicine to make the surgical outcomes much more predictable.
ABOUT DR. VAN DYKE
A world-renowned leader in translational research, who advises corporations and universities worldwide, Thomas E. Van Dyke, DDS, PhD, is currently Vice President for Clinical and Translational Research and Chair of the Department of Applied Oral Sciences at The Forsyth Institute. He is a Diplomate of the American Board of Periodontology.
