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Testimony
April 1, 2004Mr. Chairman and Members of the Committee: I am pleased to present the President's budget request for the National Institute of Dental and Craniofacial Research (NIDCR) for Fiscal Year (FY) 2005. The FY 2005 budget includes $394,080,000, an increase of $11,032,000 over the FY 2004 level of $383,048,000 comparable for transfers proposed in the President's Request. DELIVERING ON THE PROMISE OF BASIC RESEARCH Although highly technical in nature, basic research provides the detailed molecular clues that scientists and clinicians can use to develop new strategies that more effectively prevent or treat disease. This year, I would like to highlight how NIDCR's investment in the basic sciences continues to yield important advances in oral and public health. I also would like to mention how NIDCR stands to benefit from the recently launched NIH Roadmap which has the potential to catalyze virtually all areas of oral health research and, most importantly, hasten the development of novel treatments that could greatly improve American oral health. GENE TRANSFER AND THE SALIVARY GLANDS A prime example of basic research creating new clinical opportunities is the transfer of replacement genes into the salivary glands for therapeutic purposes. In the early 1990s, a team of NIDCR scientists published their initial paper on the technical feasibility of this approach. Thereafter, they began a unique long-term research interest in transferring replacement genes into the salivary glands of persons with Sjögren's syndrome and cancer patients whose salivary glands were damaged during radiation treatment. The hope was that the replacement genes would increase the production of saliva and eliminate the chronic parched sensation that plagues people with dry mouth conditions. The NIDCR scientists also began to apply their gene transfer studies to a third and seemingly less obvious therapeutic area: single-protein disorders, such as type I diabetes, human growth hormone deficiency, and erythropoietin-responsive deficiencies. Frequently overlooked in the medical literature, salivary glands not only release saliva into the mouth, they routinely secrete digestive enzymes and other proteins into the circulatory system. As the scientists later would demonstrate, the salivary glands readily accept gene-carrying vehicles, or vectors. Thereafter, with minimal coaxing, the salivary glands act as natural protein factories, dutifully manufacturing the encoded replacement protein and pumping it at steady levels into the circulation. The approach has some built in advantages over gene therapy in other parts of the body, such as the liver. Salivary glands are easily accessible and any potential adverse effects would be non-life threatening. Moreover, salivary gland cells are encapsulated to prevent leakage of the vector into the circulation and to other tissues. Recently, the group developed a new version of gene-carrying vector that entered the salivary glands of mice and produced the human protein erythropoietin for at least one year, a major step forward in the research. Just as importantly, the vector - a stripped down, bioengineered version of the harmless adeno-associated virus - did not trigger a sustained immune response, a common setback in gene therapy experiments. Building on this strong basic research base, NIDCR has developed a new initiative to evaluate the safety and efficacy of salivary gland gene transfer techniques in people with systemic single-protein deficiencies. The initiative will consist of three Phase I/II clinical trials. The first clinical trial will involve a prototype systemic single-protein deficiency disorder, adult growth hormone deficiency. As currently proposed, 21 patients will be enrolled in the study, which will be completed in four years. If successful, a second clinical trial will be conducted to treat people with erythropoietin-responsive deficiencies and ultimately a third clinical trial for those with Sjögren's syndrome and/or cancer patients with dry mouth. PERIODONTAL DISEASE AND PRETERM BIRTH Another outstanding example of basic research creating new clinical opportunities is in the area of preterm pregnancy. In the United States, about one in eight babies is born prematurelyi , which is defined as a birth that occurs three or more weeks earlier than the expected due date. As all too many parents have tragically experienced, extremely preterm babies can be so small and underdeveloped that they must remain hospitalized for months and, if they survive, spend years battling chronic health problems. This serious and common problem has spurred scientists to identify Arisk factors@ associated with premature births. These risk factors - which now include smoking, low-income status, hypertension, diabetes, alcohol use, genitourinary tract infections - allow doctors to identify women who are more likely to deliver prematurely and thereby tailor their prenatal care to control or eliminate the risk factors. However, the list of risk factors remains a work in progress. An estimated one in four preterm births occur without any known explanation, and that has left scientists searching for additional susceptibility factors to help more mothers and reduce the estimated $13.6 billion per year spent in the United States on hospital stays for infants with a diagnosis of prematurity.ii In the mid 1980s, scientists began to suspect that periodontal disease might be one of these elusive risk factors. These NIDCR grantees and colleagues monitored women with more serious periodontal disease and found they were more likely to deliver early than those with mild or non-existent disease. They also have developed a plausible biological explanation to explain the possible association. Based on animal studies, the scientists hypothesized that certain bacteria from severe periodontal infections, most notably Porphyroma gingivalis, enter the bloodstream and eventually circulate to the womb. There, the oral pathogens colonize and irritate the uterine wall. This causes inflammation of the uterus and a rise in prostaglandins and other infection-signaling chemicals, which can induce early contractions and trigger premature labor. Left unanswered is whether treating women for periodontal disease during pregnancy will help them give birth to full term babies. The NIDCR recently launched two large randomized clinical trials to answer this important public health question. These national studies, which merge the disciplines of dentistry and obstetrics, will involve over 2,600 women of various racial, ethnic, and economic backgrounds. What is unique about these clinical trials is there will be a yes-or-no outcome for each woman within 37 to 40 weeks, or the completion of the pregnancy. Women will not need to be tracked at great expense for 10 or 20 years to get the final answer, as is often the case in clinical research. Once all the data are compiled and analyzed, which could take an estimated five years to assemble and analyze, researchers anticipate that they will have sufficient clinical data to offer sound scientific advice one way or the other on this critical public health issue. PAIN RESEARCH In another example of the potential payoff from basic research, scientists are mapping in greater detail the multiple routes, or pathways, that sensory signals travel en route to the spinal cord and brain. This work has resulted in several new leads in how to more effectively manage pain. One of the most promising new leads stems from work conducted at the NIDCR. Our scientists found that an ultrapotent compound selectively eliminated an entire class of pain-sensing neurons from the peripheral nervous system of a living organism. The compound, called resiniferatoxin (RTX), killed the neurons, blocking inflammatory pain, thermal pain sensation, and reducing hypersensitivity to pain. Importantly, the animals maintained their ability to sense pain, in this case from a pinch, and they remained well coordinated, an indication that RTX did not affect sensory nerves in the muscles and joints. Since these initial reports, the investigators have assembled additional preclinical data and are moving rapidly toward evaluating RTX in human clinical trials. In order to seed additional discoveries in pain research and to help more Americans effectively manage pain, the NIDCR will begin an initiative to define the proteins and protein networks involved in processing pain-signal information in the orofacial region. This initiative encourages interdisciplinary studies that employ genomic and proteomic approaches, imaging technology, and computational biology to clarify the molecular events involved in chronic orofacial pain disorders. PUTTING RESEARCH INTO PRACTICE To achieve our goal of improved oral health for all people, NIDCR must ensure that research advances are translated and adopted into clinical practice. Many of the unique questions faced by dental health professionals on a daily basis are most appropriately addressed in dental practice settings, among unselected patient populations. Practice-based research networks can generate important and timely information to guide the delivery of health care and improve patient outcomes. The NIDCR will launch an initiative to create dental Practice-Based Research Networks (PBRNs) to conduct clinical research. In time, linking the oral health practice-based research networks with existing medical networks will provide additional patients, professional expertise, and integration of resources for conducting research across a broad spectrum of health care specialties. By connecting practitioners with experienced clinical investigators, PBRNs will enhance clinical research supported by the NIDCR and produce findings that are immediately relevant to practitioners and their patients. The networks can support a variety of clinical studies with clear and easily defined outcome measures, and they typically draw on the experience and insight of practicing clinicians to help identify and frame the questions. Because research is conducted in the real-world environment of dental practice, the results are more likely to be readily adopted by practitioners. NIH ROADMAP The NIH Roadmap provides several additional opportunities to the oral-health research community. For example the goals of the initiative Building Blocks, Biological Pathways and Networks - are closely linked to NIDCR's molecular anatomy efforts to identify the full complement of genes, proteins and protein networks that are expressed in both oral cancer and periodontal disease. Advances in proteomic analysis platforms will be crucial for NIDCR to achieve its goal of defining the salivary proteome - a critical step in the Institute's long-term goal to exploit the salivary secretions for diagnostic purposes. The Molecular Libraries and Molecular Imaging initiative holds great promise for accelerating NIDCR's progress in defining the molecular pathways of pain reception and in elucidating new therapeutic targets to manage chronic pain. In addition, the initiative Research Teams of the Future will enable NIDCR's ongoing inter- and multidisciplinary efforts to further expand and develop new ways to approach research questions. Finally, the integration of dentists into the new clinical research infrastructure that will be created by the Roadmap is key given that overall health and oral health are interrelated and that certain systemic conditions such as diabetes, Sjögren's syndrome, HIV/AIDS and osteoporosis have important oral symptoms, manifestations or complications. NIDCR envisions a clear path ahead for oral and craniofacial research. Many exciting new leads that have been reported in recent years makes it easy to imagine that the next wave of research advances will have a more profound and far reaching effect on oral health than ever before. DEPARTMENT OF HEALTH AND HUMAN SERVICES NAME POSITION BIRTHPLACE DATE EDUCATION EXPERIENCE HONORS AND AWARDS Department of Health and Human Services Mr. Beldon is currently serving as Acting Deputy Assistant Secretary for Budget, HHS. He has been a Division Director in the Budget Office for 16 years, most recently as Director of the Division of Discretionary Programs. Mr. Beldon started in federal service as an auditor in the Health, Education and Welfare Financial Management Intern program. Over the course of 30 years in the Budget Office, Mr. Beldon has held Program Analyst, Branch Chief and Division Director positions. Mr. Beldon received a Bachelor's Degree in History and Political Science from Marshall University and attended the University of Pittsburgh where he studied Public Administration. He resides in Fort Washington, Maryland. i March of Dimes Birth Defects Foundation http://peristats.modimes.org. Accessed on March 15, 2003. ii March of Dimes, PeriStats Last revised: April 12, 2004 |
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