STATEMENT OF THE HUNTINGTON'S DISEASE SOCIETY Mr. Chairman and the members of the Subcommittee, thank you for this opportunity to present our written statement regarding FY 1992 appropriations to the National Institutes of Health (NIH). Huntington's Disease Huntington's Disease is an inherited, progressively degenerative brain disorder, which results in a loss of mental and physical capacities over a period of 10 to 25 years. It is estimated that up to 1 in 5,000 live births in the U.S. have HD, and currently well over 125,000 Americans are at-risk for the disease. The HD Presently, there is no treatment or cure for this fatal disease. However, in 1983 researchers discovered a DNA marker for the HD gene, enabling many at-risk people to take a presymptomatic test to discover whether or not they will develop the disease. research model is the paradigm for many other later onset genetic disorders, such as Alzheimer's Disease, bipolar manic depression, and schizophrenia. Huntington's Disease Society of America The Huntington's Disease Society of America (HDSA) is dedicated to the detection and care of those who suffer from Huntington's Disease and to its eradication through research. HDSA also educates the professional and public communities about Huntington's Disease. Our Request Our appropriations request is based upon two objectives: to ensure that new research grants are funded, and to guarantee funding for existing projects. We at HDSA rely upon NINDS-funded grants to achieve our research goals. The HD Centers Without Walls in Maryland and Massachusetts, both funded by NINDS, are responsible for much of the innovative research on the disease. The search for the HD gene itself continues with federal funding, and the work of the federal government is bringing us closer each day to finding a cure for HD. President Bush's proposed FY 1992 budget for NINDS of $583,355,000 represents a 7.7% increase over the FY 1991 funding level. However, we believe that an even greater increase is necessary in order to sustain the level of grants at its normal current rate of progression. HDSA supports NINDS' budget request of $765,346,000 for FY 1992. This figure, the "Professional Judgment Budget, represents the amount that NINDS has determined is necessary in order to keep up with the scientific achievements of the past decade by providing funding for grants in important research areas such as Huntington's Disease. " The estimated figures for FY 1992 for HD are as follows: $ 4,326,000 for HD specifically $40,378,000 for HD and related disorders TOTAL This represents a 7% increase over 1991. The Professional Judgment Budget will aid HD research by channeling more funds to our grants, which will in turn provide much help to research in other related disorders. In recognition of the congressionally-sponsored "Decade of the Brain," we hope that Congress will continue to support the important objectives and opportunities of neuroscience research through increased appropriations to NINDS. Thank you very much for your consideration and support. STATEMENT OF THE CROHN'S AND COLITIS FOUNDATION OF AMERICA For over twenty years, America (formerly the the Crohn's & Colitis Foundation of National Foundation for Ileitis and and Colitis) has fulfilled its civic responsibility and its scientific mission by presenting testimony to the Senate House health appropriations subcommittees. Ог We have shared with you issues, concerns, and opportunities to aid the federal government fulfill its mandate to help diminish eradicate two of Our nation's chronic and devastating diseases - --Crohn's disease (ileitis) and ulcerative colitis. (These diseases are also referred to as inflammatory bowel diseases or IBD. A fact sheet about IBD is enclosed.) There have been many years when we have applauded the federal effort in this regard. For the past two years, with specific language in the House and Senate Appropriations Bills, the IBD research program of the Digestive Diseases Division of the NIDDK was strengthened. This year, we return to thank you for that heightened federal interest and for the attention you paid to Our white paper, "Challenges in IBD Research: Agenda for the 1990s," which focused the Course of IBD research and aimed to maximize effectiveness of government and private sector resources. the The "Agenda for the 1990s" white paper was the consensus of over forty recognized authorities in clinical and basic research disciplines from the United States and Canada. It outlines in considerable detail the future direction of IBD research for the next five to ten years. The NIDDK and other NIH institutes, which direct some funds to IBD-related projects, have endorsed the contents of the document. The excellent NIH and CCFA research partnership, about which CCFA has testified almost every year since its founding in 1967, has served our IBD public well. In the last few years, some sixteen out of twenty NIH researchers were initially funded by the CCFA. But now, with the advent of new technologies and insights as expressed in the "Agenda for the 1990s" white paper in the fields of genetics, immunology, and cell biology, this partnership be tested as never before. will The challenges and opportunities are now here. They are ready to be refined and to direct research down critical new pathways. New scientific pathways and proactive determination by the NIDDK in directing cystic fibrosis and diabetes research dramatically accelerated the research advances in those diseases. The impressive manner in which the NIDDK and the Cystic Fibrosis Foundation, and the American Diabetes Association and the Juvenile Diabetes Foundation, worked their research partnerships is to be applauded and emulated. In this regard, the CCFA has selected five of the many recommendations advanced in the "Agenda" document as those most suitable for the NIH and that require NIH involvement. Support of these five areas could very possibly lead to a quantum leap in IBD research. The five priorities, in rank order, which we believe merit the most serious attention from the NIH, are as follows: 1) ANIMAL MODELS. No animal model will be an exact replica of the human disease, but if one can establish that a model has complimentary features to human disease, such models can bring insight to the study of the disease in humans. For example, research into chronic arthritis and multiple sclerosis has been significantly advanced by studying immune responses in rodents. When coupled with parallel studies done in man, animal models can be a powerful means of dissecting the immune and other events going on in disease. Currently, there is a dearth of animal models of inflammatory bowel disease. Efforts should be made to develop reproducible animal models in rodents, particularly the mouse, whose immune system and genetics are the best understood of any species. These models would serve not only to help reveal the pathogenesis of disease, but also to suggest new therapies and to test new forms of immunotherapy such as the administration of cytokines, cytokine inhibitors, monoclonal antibodies to lymphocyte subsets, new drugs, and other substances. Researchers should be encouraged by various incentives to focus on the development of animal models of IBD, which we regard as pivotal to answering the riddles of these diseases. We recommend that $400,000 be made available through RFAs for the next fiscal year to provide these incentives. 2) TISSUE BANKS. Detailed basic science investigations are necessary to identify the genetic basis of IBD suggested by the genetic and epidemiological data we already have. The most important strategy for these investigations is the establishment of a comprehensive cell line bank with information correlated to a DNA and serum bank. The project could be initiated immediately. The goal would be to establish permanent cell lines in culture from 1500 to 2000 well-characterized patients with IBD, their family members, and appropriate disease-related controls. High priority would be placed on establishing cell lines from families with multiple affected cases. A consortium of institutions in New York, Chicago, and Los Angeles is already geared up to proceed with this project. With potentially 10,000 samples to be collected, a staggering amount of work is needed to investigators, and correlate data. A second strategy is to explore specific candidate genes by association and linkage studies, making use of the Human Genome Project that is mapping all human genes. The purpose of this initiative is to identify the specific genes that predispose to IBD. We recommend that $500,000 be made available through RFAs for the next fiscal year to move ahead with this project. Among the necessities are technical support, computer software, freezing equipment, and other resources. The epithelial cell has 3) EPITHELIAL CELL GROWTH AND FUNCTION. been advanced as a major player in the pathogenesis of IBD, but the normal mechanisms and regulation of epithelial cells must be better defined. Progress in understanding the role of the epithelium is partially dependent on the development of long-term intestinal epithelial culture systems. Among other advantages, these will help establish the functional significance of cell surface antigens on epithelial cells, which requires gathering a significant amount of preliminary data. In short, the function of normal epithelial cells must be clarified, and the altered function in IBD must be documented. We recommend that $500,000 be made available through RFAs for the next fiscal year to move ahead with this project. 4) SEED MONEY FOR NEW BASIC SCIENCE PROJECTS. Basic science investigators, with different perspectives relevant to disease pathogenesis and response to treatment, should be encouraged to enter the arena of IBD research. Without doubt, to make progress we need to increase available manpower to do research. Young scientists have to be recruited to make IBD their focus, and established investigators, who may be focusing on other diseases, need to be encouraged to apply their expertise and specialties to a |