Biennial and Annual Report on the Rare Diseases Research Activities at the National Institutes of Health FY 2004

Office of Rare Diseases (ORD)


The Office of Rare Diseases (ORD) was established in 1993 within the Office of the Director of the National Institutes of Health (NIH). On November 6, 2002, the President established the Office in statute (Public Law 107-280, the Rare Diseases Act of 2002). The Act defines a rare disease as a disease or condition affecting fewer than 200,000 persons in the United States and estimates that 25 million people in the United States have a rare disease.

The goals of ORD are to stimulate and coordinate research on rare diseases and to support research to respond to the needs of patients who have one of the more than 6,000 rare diseases known today. To leverage its resources, stimulate rare diseases research activities, and foster collaboration, ORD works with NIH Institutes or Centers to support

  • an extramural research program that includes a network of clinical research centers on rare diseases and the training of rare diseases researchers;
  • an intramural research program for patients with rare conditions and programs to stimulate clinical research on rare diseases, including the training of researchers interested in rare diseases and in clinical and biochemical genetics;
  • a scientific conferences program in response to scientific opportunities or to stimulate research where little exists or where research progress may have stalled;
  • an information center to supply reliable and valid information to the public, researchers, and health care providers, including various databases to provide access to information over the Web and a number of educational activities including regional workshops to assist national patient advocacy groups become partners with the NIH by developing better understanding of NIH research programs.

Scientific Advances

Extramural Research Program

  • The Rare Diseases Clinical Research Network

    Since FY 2003, ORD and several NIH Institutes and Centers support the Rare Diseases Clinical Research Network. In FY 2004, the NIH increased the number of research consortia from 7 to 10 and added support for pilot studies and demonstration projects available to each consortium. Collaborating NIH Institutes and Centers include NCRR, NHLBI, NICHD, NIAMS, NIDDK, and NINDS.

    At this time, the 33 clinical protocols are under development. The collaborating patient advocacy groups have established a coordinating coalition and are represented on the network’s steering committee. The network consists of more than 70 sites and 30 patient advocacy groups and conducts research on almost 50 rare diseases.

    The vast distribution of research locations across the United States will make investigational treatments more accessible to patients with rare diseases. The network systematically collects clinical information to develop biomarkers and new approaches to diagnosis, treatment, and prevention of rare diseases; to provide training of new clinical research investigators; and to support demonstration projects in the following rare disease groups:

    • Urea cycle disorders including citrullinemia, argininosuccinic aciduria, hyperargininemia, and others.
    • Genetic developmental disorders, including Angelman syndrome, Rett syndrome, and Prader-Willi syndrome.
    • Vasculitides including Wegener's granulomatosis, Takayasu arteritis, and Churg-Strauss syndrome.
    • Bone marrow failure including aplastic anemia, myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria, and large granular lymphocyte leukemia.
    • Rare genetic defects in steroidogenesis leading to congenital adrenal hyperplasia, androgen receptor defects, and low renin hypertension.
    • Rare lung diseases including lymphangioleiomyomatosis, alpha-1 antitrypsin deficiency, pulmonary alveolar proteinosis, and hereditary interstitial lung disease.
    • Nervous system channelopathies including Andersen-Tawil syndrome (periodic paralysis), non-dystrophic myotonic disorders, and episodic ataxias.
    • Genetic impairments in mucociliary clearance including primary ciliary dyskinesia, cystic fibrosis, pseudohypoaldosteronism, and other chronic sinopulmonary diseases.
    • Genetic causes of intrahepatic cholestasis including rare liver diseases associated with alpha-1-antitrypsin deficiency, Alagille syndrome, progressive familial intrahepatic cholestasis, bile acid synthesis defects, and mitochondrial hepatopathies.
    • Rare Thrombotic Diseases Consortium including antiphospholipid antibody syndromes, heparin-induced thrombocytopenia, paroxysmal nocturnal hemoglobinuria, catastrophic antiphospholipid antibody syndrome, and thrombotic thrombocytopenic purpura.

The three new consortia are:

1. Rare Thrombotic Diseases Consortium

Rare disorders that are associated with an increased thrombotic risk include the antiphospholipid antibody syndromes (APS), heparin-induced thrombocytopenia (HIT), combined thrombophilic states, paroxysmal nocturnal hemoglobinuria, thrombotic thrombocytopenic purpura, and the catastrophic "thrombotic storm." These disorders frequently exhibit more "aggressive" clinical phenotypes, affecting arterial, venous, and/or microvascular beds. Diagnostic and/or therapeutic limitations exist for each of these disorders, and prospective studies are needed to more clearly define the syndromes and develop better therapies. This multi-institutional academic consortium focuses on rare thrombotic disorders and will establish a Rare Diseases Clinical Research Consortium focusing on rare thrombotic disorders.

Investigators from four academic centers will bring together existing registries (e.g., The Antiphospholipid Syndrome Collaborative Registry) and programs [e.g., the Centers for Disease Control and Prevention (CDC)-sponsored Thrombophilia Programs and the Duke Center for Human Genetics] to identify and enroll patients into hypothesis-driven prospective clinical trials that focus on:

  • Genetic analysis of familial APS, familial APS/autoimmune syndromes, and patients with catastrophic "thrombotic storms."
  • Identify risk factors for thrombosis in patients with antiphospholipid antibodies and HIT.
  • Define the natural history of patients with elevated heparin-platelet factor four antibodies after bypass.
  • Emerging opportunities from ongoing studies will be identified that promote new research directions, projects, and translational activities that foster links between the consortium and industry.
  • Develop a training program for new investigators who are interested in studying rare thrombotic disorders. A program will be instituted that combines opportunities in clinical management as well as epidemiologic, genetic, diagnostic, and therapeutic investigations involving patients with rare thrombotic disorders.
  • Develop a Web site that promotes education and research activities involving patients with rare thrombotic disorders. The Web site will be developed with the Data Technology and Coordinating Center and other Rare Diseases Consortia and will be for patients, healthcare providers, and the general public.

The following sites form the consortium: Duke University Medical Center, Durham, NC; University of North Carolina at Chapel Hill, Chapel Hill, NC; University of Wisconsin, Madison, WI; Mayo Clinic, Rochester, MN; and the Centers for Disease Control and Prevention, Atlanta, GA

2. Genetic Disorders of Mucociliary Clearance Consortium

The project director will establish a Rare Diseases Clinical Research Center (RDCRC) at The University of North Carolina (UNC) and an associated consortium with three other geographically dispersed sites to study rare diseases of the airways. These four sites in the consortium will collaborate in diagnostic, genetic, and other studies in patients with genetic impairments in mucociliary clearance, specifically primary ciliary dyskinesia (PCD), variant forms of cystic fibrosis (CF), and pseudohypoaldosteronism (PHD). Patients with these unusual disorders with increased morbidity and mortality often have delayed (or incorrect) diagnoses, because diagnostic tests are not readily available. The central hypotheses are that a broad-based systematic approach to the diagnostic evaluation of these patients will yield more precise diagnostic criteria and better diagnostic techniques including genetic testing and that systematic evaluation of specific cohorts of these patients with state-of-the-art methodologies and rigorous cross-sectional and longitudinal study designs will provide better understanding of clinical pathogenesis of these disorders. In a 5-year longitudinal study of 300 patients with PCD, investigators will use innovative techniques, including measurement of pulmonary function tests and high resolution computed tomography of the chest in infants, to define early onset and progression of pulmonary disease in PCD. Moreover, 10 additional geographically dispersed sites will serve as PCD Clinical Centers to assist in the follow-up care of PCD patients in the longitudinal study. This collaborative effort will improve care by defining clinical practice guidelines, especially for PCD. The pilot projects in PCD are designed to develop better diagnostic tools, biomarkers, and screening tests; to characterize the respiratory pathobiology; and to evaluate novel therapeutic agents. The existing training program in rare airway diseases will be extended to established and young investigators. The consortium will work with the Data and Technology Coordinating Center to coordinate and expand current Web sites to provide information to the lay public, patients, and medical professionals for education, referral, and recruitment of study subjects.

The following sites form the consortium: University of North Carolina at Chapel Hill, Chapel Hill, NC; Washington University in St. Louis, MO; The Children's Hospital, Denver, CO; The Children's Hospital and Regional Medical Center, Seattle, WA.

3. Rare Liver Diseases Consortium

The investigators proposed the development of a coordinated and integrated rare liver diseases clinical research consortium. The consortium will include sites at the Children’s Hospital in Denver and clinical sites within the United States that are listed below, each with investigators who have extensive clinical experience, patient populations, and research programs for these disorders and each with a General Clinical Research Center. The consortium will focus on investigations of five genetic causes of intrahepatic cholestasis. These disorders have serious if not fatal consequences (without liver transplantation) and severely affect the children’s normal growth and development. The five related disorders are α-1-antitrypsin deficiency, Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), bile acid synthesis and metabolism defects, and mitochondrial hepatopathies.

The consortium will develop a longitudinal hypothesis-driven database study of these diseases. During this study, serum, DNA, and liver tissue will be obtained from all patients and stored for future studies. The consortium will also include:

  • biological core facilities to ensure the highest quality analysis of genetic information, liver histopathology, and bile acid biochemistry for subjects enrolled in this study;
  • a pilot/demonstration project program to encourage innovative scientific investigation;
  • a training program in order to attract new investigators to the study of rare liver diseases; and
  • development of electronic Internet-based clinical, educational, histologic, and research resources for these diseases.

Input by support/advocacy groups for these rare liver disorders will be integrated into the consortium at all levels. The consortium will be a full partner in the Rare Diseases Clinical Research Network and will participate collaboratively with the other clinical research consortia and the Data and Technology Coordinating Center.

The following sites form the consortium: The Children’s Hospital Denver, Denver, CO; Children’s Hospital of Philadelphia, Philadelphia, PA; Cincinnati Children’s Hospital Medical Center, Cincinnati, OH; King’s College, London, England; Mount Sinai School of Medicine, New York, NY; University of California/San Francisco, San Francisco, CA; and the University of Colorado Health Sciences Center, Denver, CO.

Table 1 lists the 10 consortia and the data and technology coordinating center, the principal investigators, and the primary performance site:

Table 1: The Rare Diseases Clinical Research Network

Consortium Title Principal Investigator Primary Performance Site
1. Urea Cycle Disorders Consortium Batshaw, Mark L., M.D. Children's National Medical Center,
Children's Research Institute (CNMC),
Washington, DC
2. Angelman, Rett, and Prader-Willi Syndrome Consortium Beaudet, Arthur L., M.D. Baylor College of Medicine, Houston, TX
3. Consortium for Clinical Investigations of Neurological Channelopathies (CINCH) Griggs, Robert C., M.D. University of Rochester School of Medicine, Rochester, NY
4. Idiopathic Bone Marrow Failure & Cytopenia Clinical Research Consortium Maciejewski, Jaroslav P., M.D., Ph.D. Cleveland Clinic Foundation,
Cleveland, OH
5. Vasculitis Clinical Research Consortium (VCRC) Merkel, Peter A., M.D., Ph.D. Boston University Medical Center,
Boston, MA
6. Rare Genetic Steroid Disorders Consortium New, Maria I., M.D. Weill Medical College of Cornell University at the New York Presbyterian Hospital, New York, NY
7. Rare Lung Diseases Consortium Trapnell, Bruce C., M.D. Cincinnati Children's Hospital
Medical Center (CCHMC),
Cincinnati, OH
8. Rare Thrombotic Diseases Consortium Ortel, Thomas L, M.D., Ph.D. Duke University
Medical Center
Durham, NC
9. Genetic Disorders of Mucociliary Clearance Consortium Knowles, Michael R., M.D. University of North Carolina at Chapel Hill, Chapel Hill, NC
10. Rare Liver Diseases Consortium Sokol, Ronald J., M.D. Children’s Hospital, Denver, CO
Rare Diseases Data and Technology Coordinating Center Krischer, Jeffrey P., Ph.D. H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
  • Other Extramural Research Opportunities in Rare Diseases

    ORD is cosponsoring with NIH Institutes the following research activities:

    • a Program Announcement with the NHLBI for pilot studies, demonstration projects, and/or exploratory research studies in rare diseases;
    • a Request for Applications with the NHGRI for research training grants in genomics and proteomics;
    • a Program Announcement with the NINDS to improve treatment outcomes of lysosomal storage disorders and a joint Program Announcement to support grants to provide support for the planning of phase III clinical trials;
    • ORD continued its co-sponsorship with the National Institute of Diabetes, Digestive, and Kidney Diseases of the Biliary Atresia Research Consortium, which contains nine pediatric liver disease centers. Researchers at the consortium develop and test hypotheses on the cause of biliary atresia and are defining the best means of diagnosis and management of this disease.

Intramural Research Program

The Rare Diseases Intramural Research Program is a collaboration between the ORD and the NHGRI at the NIH Clinical Center and supports a number of research activities:

  • Gynecological Aspects of Patients with Rare Diseases

    Intramural researchers established a program to evaluate gynecologic aspects of patients with Hermansky-Pudlak syndrome (HPS), cystinosis, alkaptonuria, and other rare disorders to address the issues that arise when the lives of children with previously fatal rare diseases are extended into adolescence and adulthood or as adult patients with rare diseases have gynecological complications.

  • Clinical Research Protocols

    Intramural researchers are recruiting patients with Hermansky-Pudlak syndrome (HPS) to enroll in a pirfenidone treatment protocol for the disease's fatal pulmonary fibrosis and in an NIAID sponsored diagnostic protocol for the colitis associated with HPS. HPS is a genetic metabolic disorder that causes albinism; visual impairment; a platelet dysfunction with prolonged bleeding; and progressive symptoms including pulmonary fibrosis, inflammatory bowel disease, and kidney disease.

    Intramural research led to the discovery of the gene responsible for Hartnup disorder, a rare inborn error of amino acid reabsorption. Other researchers received approval for clinical protocols, including "Genetic Analysis of Gray Platelet Syndrome (GPS)"; "Investigations of Megakaryocytes from Patients with Abnormal Platelet Vesicles" including Chediak-Higashi syndrome, Griscelli syndrome, and the newly described White platelet syndrome; and "Clinical Investigations into Autosomal Recessive Polycystic Kidney Disease (ARPKD) and Congenital Hepatic Fibrosis" for the possibility of future treatment with a tyrosine kinase inhibitor.

  • Undiagnosed Metabolic Disorders

    The Office of the Clinical Director of NHGRI, with ORD support, has begun to admit patients with rare, undiagnosed disorders. These patients are enrolled in a protocol titled "Diagnosis and Treatment of Patients with Inborn Errors of Metabolism."

  • Diagnostic Tests

    In collaboration with the NHGRI, the ORD supports a program to meet the needs of intramural investigators to establish with CLIA1-certified laboratories, molecular diagnostic tests for specific rare diseases. These tests will be made available by the developing laboratory on a fee-for-service, usually insurance-reimbursable basis, to the general public after the needs of the research investigators have been met. The first four genetic tests under development are the human phosphomannose isomerase (MPI) gene and the asparagine-linked glycosylation 6 gene (ALG6) in congenital disorders of glycosylation, the tumor necrosis factor receptor superfamily member 6 (TNFRSF6) gene associated with immune deficiency, and the methylmalonyl coenzyme A mutase (MUT) associated with methylmalonyl-CoA mutase deficiency.

    1 Clinical Laboratory Improvement Amendments

  • Research Training

    In FY 2004, the ORD supported three fellows training in Clinical and Biochemical Genetics, an important field of genetics that brings needed therapy to rare diseases patients. These fellowship opportunities provide for physicians' exposure to rare diseases research early in their careers, reinforcing their interest in and dedication to the field and thereby promoting future research experts in rare diseases. Upon completion of the training program, the research fellows will also be eligible to sit for the examination in biochemical genetics offered by the American College of Medical Genetics (ACMG). Biochemical genetics are important to develop new treatment approaches to inborn errors of metabolism, inherited disorders affecting the production and breakdown of proteins, fats, or carbohydrates.

  • Bench-to-Bedside Intramural Research Awards

    In FY 2004, ORD co-funded with NIH Institutes and Centers 11, 2-year Bench-to-Bedside awards at the NIH Clinical Center. Intramural scientists at the NIH enter into basic science-clinical research collaboration with colleagues in other NIH laboratories with a focus on rare disease. The awards included:

    • Therapeutic Application of Intra-Vascular Nitrite for Sickle Cell Disease
    • Molecular Profiling of Response to Proteasome Inhibition by Bortezomib (PS341) in a Clinical Trial of Mantle Cell Lymphoma
    • A Phase I/II Pilot Study to Evaluate the Treatment of Intraocular Lymphoma with the BL22 Immunotoxin
    • A Phase I Treatment Trial of the Circadian Sleep Disturbance in Smith-Magenis Syndrome
    • Pre-Clinical Primate Studies of an In Vivo Selectable Vector Intended for Use in a Planned Clinical Trial of Gene Therapy for Chronic Granulomatous Disease
    • Isolation and Characterization of Circulating Endothelial Cells in Primary Pulmonary Hypertension
    • Evaluation of the Humanized MiK-1 Monoclonal Antibody in Patients with HTLV-1 Associated Neurologic Disease
    • Molecular Profiling and Drug Discovery for Patients with PTEN Hamartomatous Tumor Syndromes (PHTS)
    • Immunotherapy for Myelodysplastic Syndrome
    • Intermediate Phenotype and Genetic Mechanisms for Psychosis and Cognitive Disturbance in 22q11.2-hemideletion Syndrome
    • Childhood Cancer and Plexiform Neurofibroma Tissue Microarray for Molecular Target Screening and Clinical Drug Development

    ORD also continued to support five bench-to-bedside awards in their second year. Those research projects focused on Williams syndrome, hereditary inclusion body myopathy, acute lymphoblastic leukemia, pulmonary sarcoidosis, and leukemogenesis.

Education, Public Information, and Public Input

  • Genetic and Rare Diseases Information Center

    The ORD supports with the NHGRI the Genetic and Rare Diseases Information Center (GARD). The information center provides information to patients and their families, health professionals, researchers, and the public. In FY 2004, the information center became more accessible to minority and underserved populations through services in Spanish in addition to English and a more user-friendly Web-based approach. Since its inception in September 2001, the Information Center has responded to more than 10,000 inquiries for more than 3,000 rare diseases.

  • Combined Health Information Database (CHID)

    ORD supported the Medical Genetics and Rare Disorders subfile of the Combined Health Information Database (CHID). The subfile provides information about and available from patient advocacy groups. In 2004 and 2005, ORD is reviewing, updating, and expanding the subfile through a contract with the National Organization for Rare Disorders. At this time, 8,178 indexed documents are in the subfile as well as 1,302 organizations. 4,352 searches were conducted specifically against the subfile in addition to the approximately 1,057,807 searches across CHID as a whole (a total of 11 subfiles.)

    Genetics Education for Healthcare Providers:

  • National Coalition for Health Professional Education in Genetics (NCHPEG)

    ORD also supported the National Coalition for Health Professional Education in Genetics (NCHPEG). Established in 1996 by the American Medical Association, the American Nurses Association, and the NHGRI, NCHPEG is a national effort to promote health professional education and access to information about advances in human genetics. NCHPEG members are an interdisciplinary group of leaders from approximately 120 diverse consumer and voluntary groups, medical societies, government agencies, private industry, managed care organizations, and genetics professional societies. By promoting frequent and open communication between stakeholders, NCHPEG seeks to capitalize on the collective expertise and experience of members and to reduce duplication of effort.

    As patients ask more questions about genetic tests and disease risk, more responsibility for the use and interpretation of genetic tests and information will fall to primary care physicians, nurses, physician assistants, advanced practice nurses, and other health professionals who may not be formally trained in genetics. This is of importance to ORD since it is estimated that 80 percent of rare diseases have a genetic basis. Core competency educational materials have been produced in English and in Spanish.

    NCHPEG is currently coordinating "Genetic Resources on the Web (GROW)" a source of quality information about human genetics for health professionals and the public. ORD co-founded GROW with other NIH components and Federal agencies. A first training module for genetics for health professionals has been developed for dentists and dental hygienists. The second module is directed toward genetic counselors for a better understanding of genetics and psychiatric disorders. The next module to be completed with the American Academy of Family Physicians will be for physicians in family practice.

    Public Input

    ORD continued to support the annual meetings of the Genetic Alliance and the National Organization for Rare Disorders (NORD). These two umbrella organizations represent collectively more than 600 rare diseases patient advocacy groups. ORD utilized these meetings to conduct focus groups to determine the needs of member organizations and to identify programs ORD should consider implementing. Also, NIH research scientists and ORD staff are active participants in all sessions of the annual meetings and disseminate information about NIH rare diseases research programs.

    In FY 2004, ORD continued to support regional workshops to discuss with leaders of patient advocacy groups across the nation all aspects of research and research opportunities in NIH’s extramural and intramural research programs. These workshops enable national patient advocacy groups to become partners in research endeavors. To gain public input into ORD program plans, ORD held focus group meetings with leaders of patient advocacy groups at the annual meetings of the NORD and the Genetic Alliance.

Identifying Future Research Opportunities for Rare Diseases

ORD collaborates with Institutes, Centers, and Offices at NIH and other Federal agencies to stimulate rare diseases research by co-sponsoring scientific conferences where research is lagging or to take advantage of scientific opportunities. The outcomes of these scientific conferences have included the establishment of research priorities, development of collaborative research protocols, criteria for diagnosing and monitoring rare diseases, specific discoveries, publications, and new research endeavors. These scientific conferences have also contributed to the exchange of ideas and information among basic and clinical investigators, patient advocacy groups, NIH staff, and the pharmaceutical industry.

In FY 2004, ORD co-funded 87 national and international scientific conferences. Examples of the scientific conferences in FY 2004 include childhood cancers, bone marrow failure, sickle cell disease, congenital heart disease, dystonias, pediatric stroke, neurofibromatosis, and primary lateral sclerosis. A list of the scientific conferences is provided in the appendix.

New and Future Initiatives

ORD has a number of future initiatives and began a number of major new initiatives that will continue and come into fruition in the coming years.

Coordination of Rare Diseases Research Activities

  • Trans-NIH Rare Diseases Research Working Group

    The ORD established a Trans-NIH Rare Diseases Research Working Group. Currently the membership encompasses NIH ICs and the Food and Drug Administration’s Office of Orphan Products Development. In the future, liaison membership will be expanded to include other Federal agencies and representatives of rare diseases federations. In the coming year, the working group is developing plans for a conference on rare diseases biospecimen collection, storage, and delivery issues that impede research on rare diseases. Other issues under review include expansion of the development of genetic testing in NIH extramural research programs and a conference on amyloidosis.

  • Exploratory and Developmental Research Grants for Investigations in Rare Diseases

    The ORD currently participates with the NHLBI in an announcement for Exploratory and Developmental Research Grants for Investigations in Rare Diseases. The purpose of this announcement defines the scope of exploratory and developmental grant applications to the NHLBI for support of investigators with novel approaches to understanding, treating, and preventing rare diseases in the areas of heart, lung, and blood disease as well as sleep disorders. In FY 2005, ORD will co-fund applications in these rare diseases. Availability of these awards for these individuals is expected to allow investigators with novel ideas to obtain research support without the need for large amounts of preliminary data that often serves as a barrier to entry into the NIH grants system. It is anticipated that these efforts will ultimately result in an increased pipeline of therapeutic approaches to treatment and prevention of rare diseases. Rare diseases are often referred to as "orphan" diseases since there is a general lack of interest among industries to invest resources in diseases that in aggregate comprise too small a population to guarantee return on investment. The ORD would like to expand this program to include other ICs. Partners for each project would be solicited to expand the co-funding throughout the NIH.

  • Diagnostic Testing

    In response to recent concerns about the lack of diagnostic tests for rare diseases, ORD is evaluating this situation. There are more than 6,000 rare diseases, and the majority of the rare diseases are considered genetic, making genetic testing an essential part of the diagnosis and treatment continuum. Currently, genetic testing for rare diseases is only available for a small number of diseases and may only be available through a research laboratory or a laboratory overseas. Developing and marketing tests is not profitable because of a small number of consumers, and there are no incentives to translate research findings into clinical tests.

    To address this need, the ORD initiated in the intramural research program that it sponsors together with the National Human Genome Research Institute a pilot program to bring tests to market by contracting with commercially based and academic center-based, CLIA-certified laboratories.

    ORD brought this pilot program to the attention of the Trans-NIH Rare Diseases Research Working Group. The working group was very interested in the outcomes of the pilot program and began discussing means by which such an approach could be applied to extramural programs in the future.

    In a parallel move, the ORD collaborated with the Centers for Disease Control and Prevention, Emory University, the American Society for Human Genetics, the American College of Medical Genetics, the Health Resources and Services Administration, and the Genetic Alliance to hold a conference titled “Promoting Quality Laboratory Testing for Rare Diseases: Keys to Ensuring Quality Genetic Testing.” Deliberations led to a number of recommendations and planning activities, which will culminate in a follow-up conference to integrate recommendations into actions and projects in 2005. ORD with the ICs will develop a plan to develop the needed infrastructure for the development of genetic tests for research purposes that would meet CLIA standards.

  • Patient Travel to Research and Treatment Sites

    ORD and NHGRI have jointly invited Mercy Medical Airlift to participate in the NIH Clinical Center rare diseases efforts. This not-for-profit organization facilitates transportation free of charge to and from the Clinical Center for patients enrolled in rare disease research protocols and one or two family members. ORD expects expansion of this activity to include the Rare Diseases Clinical Research Network and possibly for travel to research protocols for the U.S. population.

  • Amyloidosis

    Amyloidosis is a group of devastating diseases in which one or more organ systems in the body accumulate abnormal proteins. In primary amyloidosis, the heart, lung, skin, tongue, thyroid gland, and intestinal tract may be involved as well as the liver, spleen, kidney, and the vascular system, especially the heart. Secondary amyloidosis usually affects the spleen, liver, kidney, adrenal glands, lymph nodes, and the vascular system. Hereditary amyloidosis is characterized by peripheral sensory and motor neuropathy, autonomic neuropathy, and cardiovascular and renal involvement. ORD will develop a plan to respond to Congressional concerns and as part of the initiative will cosponsor a conference with NIH ICs.

  • Rare Diseases Biospecimen Repositories

    The issue of availability of high-grade biospecimen and clinical data for research constitutes a barrier to rare diseases research. ORD funded a demonstration project with the National Disease Research Interchange (NDRI) and brought this issue to the attention of the Trans-NIH Rare Diseases Research Working Group. The Genetic Alliance has moved to establish a “biobank” for which it charges patient advocacy groups appropriate fees to participate and to maintain the biospecimens that are DNA. However, many rare diseases groups do not have the funds for such an endeavor, and many more rare diseases do not have an advocacy group. A number of organizations have expressed interest in accommodating rare diseases research, but a comprehensive examination of the issues is needed. The Trans-NIH Rare Diseases Research Working Group has formed a planning committee to determine the issues that need to be explored and to identify the significant players of biospecimen collection, storage, and dissemination. The planning committee will provide recommendations to the NIH for a conference that will lead to a clear understanding of the needs and a plan for implementation.

Identifying Future Research Opportunities for Rare Diseases

In FY 2005, ORD will cosponsor approximately 100 scientific conferences. At this time, 58 scientific conferences have been approved (see Table 3 in the appendix for a list of topics), with another two application cycles throughout FY 2005.

Genetic and Rare Diseases Education

  • Rare Diseases Information

    The ORD Web site provides information about biomedical research, scientific conferences, and rare diseases and is a portal to information on major topics of interest in the rare diseases community. The ORD will participate in a Web site user satisfaction survey to further improve the outreach to and delivery of information to patients with rare diseases.

    The Genetic and Rare Diseases Information Center will provide additional services in Spanish and will, together with ORD and NHGRI, continue outreach efforts to underserved populations.

  • Education of Leaders of Patient Advocacy Groups

    In January 2005, ORD will conduct a regional workshop in Philadelphia for 55 leaders of national patient support organizations. In the past, ORD conducted regional workshops in New York and in San Francisco for more than 85 leaders of national patient advocacy groups to assist the support groups in being an active participant in the rare diseases research enterprise by getting a better understanding of the structure and function of the NIH and the Food and Drug Administration (FDA).

  • A Database of National and International Patient Advocacy Organizations

    ORD supports the Medical Genetics and Rare Disorders subfile of the Combined Health Information Database (CHID). In 2005 and 2006, ORD is reviewing, updating, and expanding the subfile to include English and Spanish speaking international patient advocacy organizations and their publications, through a contract with the National Organization for Rare Disorders. The database will expand to include many more international organizations with an emphasis on rare diseases.

Outreach to the Latino Communities

The National Human Genome Research Institute, the ORD, and The National Council of La Raza’s Institute for Hispanic Health will partner in a pilot education project to demonstrate efficient ways to reach Latino communities with information about genetic and rare diseases.


Table 2: ORD Cosponsored Scientific Conferences in FY 2004

Primary Cosponsor Title
  • Cockayne Syndrome and Related Disorders of DNA Repair and Transcription: From Bench to Bedside and Back
  • Mechanisms of Alcohol-associated Cancer Symposium
  • Transplantation Immunology
  • International Conference on Burkholderia Pathogenesis: Approaches and Opportunities for Research on Glanders and Melioidosis
  • Biology of Calpains in Health and Disease
  • Intermediate Filaments
  • Mild Osteogenesis Imperfecta: Toward Better Understanding and Treatment
  • New Directions in Biology and Disease of Skeletal Muscle
  • Pathogenic Mechanisms of Fibrosis: Search for Common Ground
  • Pseudoxanthoma Elasticum Research Meeting 2004: Building on the Basics
  • 19th International Pigment Cell Conference: A Focus on Human Pigmentary Disorders
  • Thrombospondins and Other Modulatory Adhesion Molecules in Tissue Organization
  • ATP Binding Cassette Gene
  • Biliary Tract Cancer
  • Cancer Survivorship: Genetic Susceptibility and Second Primary Cancers
  • Childhood Cancer: Improving Care After Treatment
  • Collaborative Approaches to Discovering Genes in African Americans and Hispanics Utilizing Mapping by Admixture Linkage Disequilibrium
  • First NIH Peritoneal Mesothelioma Meeting
  • Global Increases in Esophageal Adenocarcinoma: Current Epidemiologic Research and Future Directions
  • Lymphangiogenesis and Cancer Workshop
  • NIH Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-host Disease
  • RNA Interference: Target Validation and Potential Therapeutic Applications for Childhood Cancers
  • Sarcoma and Mesenchymal Stem Cell Biology
  • Malformation/Morphogenesis
  • Children with Special Needs: Planning a Research Future
  • Collaborative Genetic Disease Research: Needs and Opportunities
  • Cornelia de Lange Syndrome
  • Fetal Therapy: Needs Assessment and Future Directions
  • Molecular Aspects of Infection and Inflammation—Common Pathways, Rare Pediatric Diseases
  • Pineal Cell Biology
  • Reproduction and the Fragile X Premutation
  • Signaling in Vertebrate Organogenesis
  • The World Congress on Chromosome Abnormalities
NIH Clinical Center
  • Functional Genomics of Critical Illness and Injury
  • Universal Reporting Parameters for the Speech of Individuals with Cleft Palate
  • Protein Misfolding and Misprocessing in Disease
  • Multiple Endocrine Neoplasias
  • Workshop on Bioiron, Thalassemia, Sickle Cell Disease, and Hemochromatosis
  • Advancing Diagnostic Approaches for TMJ Diseases and Disorders
  • Assessing Human Germ Cell Mutagenesis in the Post-genome Era
  • Environmental Neuroscience
  • Mold-related Health Effects: Clinical, Remediation Worker Protection, and Biomedical Research Issues
  • Central Nervous System Lymphoma
  • The First International Symposium on Translational Clinical Research for Inherited and Orphan Retinal Diseases
  • International Pulmonary Hypertension
  • A Consultative Network for Sickle Cell Disease
  • Bone Marrow Failure
  • Frontiers of Knowledge in Sleep and Sleep Disorders: Opportunities for Improving Health and Quality of Life
  • Inflammation and Immunity in Dilated Cardiomyopathy
  • Molecular Mechanisms in Lymphatic Function and Disease
  • Needs and Opportunities to Study Hypersensitivity Pneumonitis
  • Pediatric Interstitial Lung Disease International Research Conference
  • Second Annual International Pulmonary Alveolar Proteinosis Research Conference
  • The Lymphangioleiomyomatosis Foundation International Research Conference
  • Research in Adult Congenital Heart Disease
  • Engaging Latino Communities in the Future of Genomics Science
  • Gene Therapy for Wiskott-Aldrich Syndrome: Current Status and Plans for the Future
  • New Direction for Sickle Cell Therapy in the Genome Era
  • Holoprosencephaly (HPE): Midline and Laterality
  • First NIH-ORD Conference on Cystinosis: Past, Present, and Future
  • First International Symposium on N-Acetylaspartate (Canavan Disease)
  • Pragmatic Considerations of Culture and Prevention of Suicide
  • Rehabilitative Approaches to Dystonia
  • WORLD Lysosomal Diseases Clinical Research Network
  • Brain Uptake and Utilization of Fatty Acids, Lipids, and Lipoproteins: Applications to Neurological Disorders
  • Calcium and Cell Function
  • Clinical Trials in Spinal Muscular Atrophy
  • Developing Therapies for the Neurofibromatoses
  • Neurofibromatosis Research Program
  • Drug Screening for Ataxia-Telangiectasia
  • First International Conference on Ideomotor Apraxia
  • Pathogenesis and Treatment of Periodic Paralyses
  • Scientific and Clinical Symposium on Tourette Syndrome
  • Frontotemporal Dementia and Pick’s Disease
  • Glutamic Acid Decarboxylase Autoimmunity in Batten Disease
  • Rare Neuroimmunologic Disorder
  • The Glycoproteinoses: An International Workshop on Advances in Pathogenesis and Therapy
  • Developmental Brain Injury
  • International Trial Network on Duchenne Muscular Dystrophy
  • Primary Lateral Sclerosis
  • Toward the Development of Pediatric Stroke Trials
  • Developing the Capacity for End of Life and Palliative Care Research
  • Increasing Opportunities in Biobehavioral Research Utilizing Allergic Bronchopulmonary Aspergillosis as a Framework
  • Promoting Research on Focal Cognitive Deficits in Non-dementing Disorders
  • Promoting Quality Laboratory Testing for Rare Diseases: Key to Insuring Quality Genetic Testing

Table 3: ORD Cosponsored Scientific Conferences so far in FY 2005

Primary Cosponsor Title
  • Human Mitochondrial Diseases
  • Mechanisms of Alcohol-induced Hepatic Fibrosis
  • Pulmonary Nontuberculous Mycobacterial Infections: Phenotype and Genotype of an Autosomal Dominant Disorder Primarily Affecting Older Women
  • The Molecular Biology of Spirochetes
  • Gordon Conference on the Biology of Spirochetes
  • Treatment of Neurocysticercosis
  • Eosinophil-associated Disease: Approaches to Treatment
  • Collaborative Immune Studies in Leprosy
  • Hydatidosis–New Approaches to Vaccines and Prevention
  • Human African Trypanosomiasis: Strategic Research Direction
  • Burden of Muscle Disease
  • The 4th International Congress on Systemic Autoinflammatory Diseases
  • NCI-MMHCC Working Group on Brain Tumors
  • Kidney Cancer–Current Perspectives and Future Directions
  • Translational Genomics of Neuroblastoma
  • NIH Development Project on Criteria for Clinical Trials in Chronic Graft-versus-host Disease–Final Open Conference
  • Biology and Therapy for Malignant Salivary Gland Tumors
  • Cancer Risk in Relatives in Ataxia-Telangiectasia Patients
  • Liver Cancer in the United States
  • Bloom Syndrome: Molecular Basis of Genomic Instability
  • Poverty and Cancer: AIDS-Related Malignancy
  • Mechanisms of Follicular Dysfunction in Ovarian Insufficiency and Premature Ovarian Failure
  • First International Symposium on Pheochromocytoma
  • Artificial Reproductive Technology and Adverse Pregnancy Outcomes
  • 9th International Conference on Osteogenesis Imperfecta
  • Oxygen in Babies
  • Collaborative Genetic Disease Research: Needs and Opportunities
  • Near-term Pregnancy and Near-term Newborn Infant: Optimizing Care and Long-term Outcomes
NIH Clinical Center
  • Role of Nitrite in Physiology, Pathophysiology, and Therapeutics
  • Sjögren’s: Transition from Autoimmunity to Lymphoma
  • Familial Amyloidotic Polyneuropathy and Other Transthyretin Related Disorders and the Liver Transplantation in Familial Amyloidotic Polyneuropathy
  • Primary Sclerosing Cholangitis: Research Workshop
  • Inherited Metabolism Disorders
  • Gene/Environment Interactions in Rare Diseases that Include Common Birth Defects
  • Ion Channel Regulation
  • Conference on Environmental Mutagens
  • Physiological Genomics of Critical Illness
  • Resources for Late-stage Drug Development for Hemoglobin Disorders
  • Refinement of Hemoglobin Gene Transfer Vectors and Approaches for Clinical Application to Sickle Cell Disease and Cooley’s Anemia
  • Hemoglobinopathy Working Group
  • Meeting of the National Sickle Cell Disease Program
  • Cooley’s Anemia Symposium
  • International Kawasaki Disease Symposium
  • Cardiovascular Development Conference
  • Working Group on Cardiomyopathies of Rare Diseases
  • Hermansky-Pudlak Syndrome
  • Autosomal Recessive Polycystic Kidney Disease
  • Smith-Magenis Syndrome Research Roundtable Symposium
  • Indigenous Suicide in the Americas
  • Tuberous Sclerosis Complex
  • Neurodegeneration with Brain Iron Accumulation
  • Neuronal Ceroid Lipofuscinosis
  • CAG Triplet Repeat Disorders
  • Research Planning Workshop on Spasmodic Dysphonia
  • Hydrocephalus: Myths, New Facts, Clear Directions
  • Vascular Cognitive Impairment: Harmonization Criteria
  • Research Issues in a Multicultural Society HIV/AIDS as a Case Study
  • Dietary Supplements, Coagulation, and Antithrombotic Therapies


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Last Reviewed: July 22, 2005