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Extramural Research Program

NIH Establishes Rare Diseases Clinical Research Network

Rare Diseases Clinical Research Network

On February 27, 2003, ORD in response to the Rare Diseases Act of 2002, P.L. 107-280, released a Request for Applications (RFA) for a Rare Diseases Clinical Research Network together with the National Center for Research Resources (NCRR)/General Clinical Research Consortium (GCRC) Program and in collaboration with other NIH Institutes. ORD, NCRR, and the National Institute of Child Health and Human Development (NICHD), National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Heart, Lung, and Blood Institute (NHLBI), all components of the NIH, funded eight rare diseases clinical research consortia and one Data and Technology Coordinating Center.

The purpose of the network is to facilitate clinical research in rare diseases through

  • Collaborative clinical research in rare diseases, including longitudinal studies of individuals with rare diseases, clinical studies, phase one and two research studies, and/or pilot and demonstration projects to respond to the very differing level of research and to facilitate research that is sorely needed;
  • Training of clinical investigators in rare diseases research;
  • Clinical data management that incorporates novel approaches and technologies for data management, data mining, and data sharing across rare diseases, data types, and platforms; and
  • Access to information for basic and clinical researchers, academic and practicing physicians, patients, and the lay public across the U.S. and abroad. This cooperative program should facilitate many advances including the identification of biomarkers for disease risk, disease severity/activity, and clinical outcome and encourage development of new approaches to prevention, diagnosis, and treatment of many rare diseases beyond those being studied. The easy and free availability of data from the Data and Technology Coordinating Center should also spawn many new research ideas and subsequent applications to NIH Institutes and Centers.

Abstracts of the funded applications follow:


Title of Project:

Principal Investigator/Project Director:
Contact Information:

Urea Cycle Disorders Consortium

Batshaw, Mark L, M.D.
Children's Research Institute,
111 Michigan Avenue, NW
Washington, D.C.

Description from the Grant Application:
We propose to establish a Rare Disease Clinical Research Consortium (RDCRC) at the Children's National Medical Center (CNMC) in Washington, D.C. The RDCRC will draw support from both the Pediatric General Clinical Research Center at CNMC/Georgetown University Medical Center (GUMC) as well as its Mental Retardation and Developmental Disabilities Research Center (MRDDRC). The unifying clinical theme of the RDCRC is the study of urea cycle disorders (UCD). This RDCRC will consist of a network of five academic institutions, each of which has GCRC/MRDDRCs [CNMC/GUMC, Children's Hospital of Philadelphia, Vanderbilt University, Baylor Medical Collage and University of California at Los Angeles]. The proposed RDCRC will comprise a multidisciplinary team of 10 investigators in the following specialties: Genetics, Metabolism, Developmental Pediatrics, Clinical Pharmacology, Neurology, Psychology, Biostatistics, and Neuroimaging. Mark L. Batshaw, M.D., the Director of the CNMC MRDDRC, will serve as Principal Investigator, and Mendel Tuchman, M.D., Director of the PCRC at CNMC, will serve as Co-Director.The primary goals of the RDCRC are to

  • Establish a registry and nationwide consortium of regional centers for the diagnosis, treatment and clinical research in UCD;
  • Conduct a longitudinal study to determine the natural history of UCD;
  • Conduct a clinical trial of an investigational new drug (IND), N-carbamyI-L-glutamate, for treatment of these disorders;
  • Conduct a demonstration/pilot project to develop a novel method for measuring in vivo ureagenesis in UCD that will be important for diagnosis and classification of patients and for evaluation of treatment efficacy;
  • Train graduate students, pediatric residents, clinical fellows and junior faculty members in the field of inborn errors of metabolism; and
  • Develop and maintain UCD website content that will:
    1. include guidelines for health care providers regarding diagnosis and treatment;
    2. provide information to the lay public regarding consultation and treatment at major centers; and
    3. provide links to recent scientific literature for interested investigators.
This initiative will be undertaken in close collaboration with the National Urea Cycle Disease Foundation (NUCDF), the leading public advocacy organization for this group of diseases.

Performance Sites:
Children's National Medical Center, Children's Research Institute (CNMC), Washington, D.C.
Georgetown University Medical Center (GUMC), Washington, D.C.
Children's Hospital of Philadelphia (CHOP), Philadelphia, PA
Vanderbilt University (VU), Nashville, TN
Baylor Medical College (BMC), Houston, TX
University of California at Los Angeles (UCLA), Los Angeles, CA

Patient Support Organization:
National Urea Cycle Disorders Foundation (NUCDF)


Title of Project:

Principal Investigator/Project Director:
Contact Information:

Angelman, Rett & Prader-Willi Syndrome Consortium

Beaudet, Arthur L, M.D.
Baylor College of Medicine,
One Baylor Plaza,
Houston, TX 77030

Description from the Grant Application:
This is an application from an inter-institutional group of investigators with long-standing interest in Rett syndrome, Angelman syndrome (AS), and Prader-Willi syndrome (PWS) to establish a Rare Diseases Clinical Research Consortium (RDCRC) that would be part of the proposed Rare Diseases Clinical Research Network (RDCRN). The consortium will focus on these three disorders with the expectation that they may have near-term potential for meaningful therapy. The specific aims for Rett will be to establish a phenotype/genotype correlation over a broad spectrum of Rett phenotypes, to perform longitudinal studies on a broad sample of individuals with Rett, and to perform a survival study on a broad spectrum of Rett individuals. Clinical trials may be developed based on results of studies of animal models. The specific aims for AS are to conduct a longitudinal assessment of patients with AS according to genotype, to complete the ongoing double-blind, placebo controlled trial of folic acid and betaine in AS, and to develop a follow-on clinical trial for activation of the paternal allele for UBE3A in AS patients. The specific aims for PWS are to conduct longitudinal studies according to genotype, to develop parameters and tools for clinical trials, to test whether autistic features are more frequent in UPD than in deletion cases, and other ideas from collaborators. The aim of a pilot project using comparative genomic hybridization (CGH) on microarrays would be to develop a cytogenetic test that would detect all sizable deletions and duplications of clinical relevance on a single analysis using CGH microarrays. This new methodology would also have the potential to identify new deletion and duplication syndromes. The RDCRC will utilize GCRCs in Houston, Boston, San Diego, Gainesville, and other locations. The consortium is expected to function synergistically with the Mental Retardation Research Center (MRRC) at Baylor. An extensive program is proposed for training new investigators in clinical research on rare diseases. The consortium will have active affiliation with the International Rett Syndrome Association (IRSA), the Angelman Syndrome Foundation (ASF), and the Prader-Willi Syndrome Association (PWSA). It is anticipated that the RDCRC will expand to include other geographic sites for the three diseases to be studied initially, and it is expected that the Center can also expand to include other disorders, such as inborn errors of metabolism amenable to hepatocyte gene therapy, disorders treatable by enzyme replacement therapy, CHARGE association, incontinentia pigmenti, Smith-Magenis syndrome, Xp deletion syndromes, and other chromosomal deletion and duplication syndromes.

Performance Sites:

Baylor College of Medicine, Houston, TX
Greenwood Genetic Center, Greenwood, SC
University of Alabama, Birmingham, AL
University of Florida, Gainesville, FL
Children's Hospital, Boston, MA
Children's Hospital, San Diego, CA
University of California, Irvine (UCI) Medical Center, Orange, CA

Patient Support Organizations:
International Rett Syndrome Association (IRSA)
Angelman Syndrome Foundation (ASF)
Prader-Willi Syndrome Association (USA), (PWSAUSA)


Title of Project:

Principal Investigator/Project Director:
Contact Information:

Consortium for Clinical Investigations of Neurological Channelopathies (CINCH)

Griggs, Robert C, M.D.
University of Rochester Medical Center
Department of Neurology
601 Elmwood Avenue, Box 673
Rochester, NY 14642

Description from the Grant Application:
This application proposes to investigate three rare neurological channelopathies: periodic paralysis, non-dystrophic myotonic disorders, and episodic ataxia. The research plan will exploit the strengths of seven collaborating centers to link molecular scientists studying these disorders with clinical investigators with established expertise in the development of new treatments for neurological disease. It will extend a prototype NIH training program in experimental therapeutics to train a cadre of patient-oriented-researchers committed to rare disorders. Study investigators have strong links with the patient advocacy organizations focused on these rare disorders: The Periodic Paralysis Association, the National Ataxia Foundation and the Muscular Dystrophy Association. A particular strength of the collaborating institutions is an established nationwide infrastructure, including GCRCs and a biostatistician, for the implementation of multicenter clinical trials that will facilitate investigation of the efficacy of putative new treatments for rare diseases.

Currently-funded studies of the pathophysiology of the three specific target diseases will provide resources for molecular characterization of subjects and make it possible to:

  1. Begin the characterization of the phenotype/natural history of each;
  2. Devise outcome measures for treatment trials;
  3. Assess quality of life -- all in preparation for pilot clinical trials of novel treatments.

The focus of investigation is on:

  1. Andersen-Tawil syndrome, a periodic paralysis with associated life-threatening cardiac arrythmias for which no treatment has been identified;
  2. The non-dystrophic myotonias caused by sodium and chloride channel mutations for which there is no established treatment and there have been no well-designed clinical trials;
  3. The episodic ataxias EA1 and EA2 for which treatment is not yet defined.

Both cellular model systems and animal models, funded separately, are/or soon will be available for each of these disorders and can provide preclinical data necessary for proposed phase one and two trials of novel treatments. These three disorders are prototypes for the development of treatment strategies for more than 50 other rare neurological channelopathies. They may also offer a window for understanding more common disorders likely to be caused by CNS channel mutations/dysfunction such as migraine and epilepsy.

Performance Sites:
Brigham and Women's Hospital, Boston, MA
National Institute of neurological Diseases and Stroke, NIH
University of California, Los Angeles, CA
University of California, San Francisco, CA
University of Kansas Medical Center, Kansas City, KS
University of Rochester School of medicine, Rochester, NY
University of Texas Southwestern Medical Center at Dallas, TX

Patient Support Organizations:

Periodic Paralysis Association (PPA)
National Ataxia Foundation (NAF)
Muscular Dystrophy Association (MDA)


Title of Project:

Principal Investigator/Project Director:

Contact Information:

Idiopathic Bone Marrow Failure & Cytopenia Clinical Research Consortium

Maciejewski, Jaroslav P, M..D., Ph.D.
Cleveland Clinic Foundation
Department of Experimental Hematology and Hematopoiesis
9500 Euclid Avenue, Cancer Center, R40
Cleveland, OH 44195

Description from the Grant Application:
Idiopathic bone marrow failure states and cytopenias (IBMFS&C;) are rare disorders characterized by hematopoietic progenitor or stem cell failure resulting in deficient production of one, or all, blood cell lineages. Immune pathophysiology is a unifying factor in many cases of all these diseases. Prior collaborative trials have led to the improvement of effective medical therapy for aplastic anemia (AA), but ongoing multicenter studies are required to advance further the outcome for AA and especially the other bone IBMFS for which few useful treatment options exist. The IBMFS&C; Rare Disease Clinical Research Consortium (RDCRC) at The Cleveland Clinic Foundation (CCF) Cancer Center, will encompass a consortium of several specialized centers, patient advocacy group, and data and a collaboration with a data technology coordinating center (DTCC), the IBMFS&C; RDCRC will focus on AA, paroxysmal nocturnal hemoglobinuria, single-lineage cytopenias including large granular lymphocyte leukemia and pure red cell aplasia, and various myelodysplastic syndromes. This proposal presents a multi targeted approach to improving the medical therapy for IBMFS&C; that includes:

  • Implementing treatment algorithms for each IBMFS that define standards of care.
  • Systematically evaluating novel laboratory assays that may improve the diagnostic accuracy or understanding of pathophysiologic mechanisms.
  • Enrolling patients into a longitudinal follow-up study to correlate new and established diagnostic variables with outcome.
  • Comparing medical and transplant approaches for each relevant disorder.
  • Developing experimental treatment protocols for disease subsets currently without good treatment options or without a standard treatment approach.
  • Training of postdoctoral fellows to develop clinical trials and translational research projects for the IBMFS&C.;
  • Educating community physicians in the diagnosis and management of the IBMFS&C;, and
  • Improving outreach, education and referral resources for patients and physicians, in collaboration with the Aplastic Anemia & MDS International Foundation (AAMDSIF).
Due to the expertise of the PI, together with the experience and size of CCF, CC, CCF, uniquely is positioned to serve as an RDCRC in IBMFS&C.; A number of leading experts formed a consortium of medical centers that will be an integral part of the RDCRC. To support further its activities, additional infrastructure for this effort will include a formation of a rare disease office in each of the centers of the consortium, specialized laboratory testing sites, oversight of clinical trials, data management by the DTCC, and patient referral and education by the AAMDSIF. The IBMFS&C; RDCRC and the consortium have developed a plan for educating fellows and community physicians about IBMFS&C.; The success of these efforts will be evaluated in part by tracking referrals to the participating centers for standard treatment, or enrollment in the longitudinal and treatment protocols.

Performance Sites:
The Cleveland Clinic Foundation, Cleveland, OH
UCLA Department of Hematology and Oncology, Los Angeles, CA
The Penn State Cancer Institute, Milton S. Hershey Medical Center, Hershey, PA
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Aplastic Anemia and Myelodysplasia International Foundation, Annapolis, MD

Patient Support Organization:
Aplastic Anemia and MDS (Myelodysplasia Syndromes)International Foundation, Inc.
Paroxysmal Nocturnal Hemoglobinuria (PNH) Support Group


Title of Project:

Principal Investigator/
Project Director:

Contact Information:

Vasculitis Clinical Research Consortium (VCRC)

Merkel, Peter A, M.D., Ph.D.

Boston University School of Medicine
Arthritis Center
715 Albany Street, Evans 501
Boston, MA 02118

Description from the Grant Application:

Aim 1, Establish a multicenter Vasculitis Clinical Research Consortium (VCRC) to foster and facilitate clinical investigation in the inflammatory vasculitides. The four major US vasculitis centers (Boston University, Cleveland Clinic, Johns Hopkins, and Mayo Clinic) will combine their clinical and research expertise with the resources of the General Clinical Research Centers at each site to form the core of the consortium. Additionally, the combined strengths of several domestic and foreign secondary centers will be incorporated into the consortium. The VCRC would serve as the focal point for vasculitis research in the United States and internationally for both clinical investigators and patients. To achieve this aim, the following activities are proposed:
  • Develop a clinical data repository in collaboration with other Rare Disease Clinical Research Consortia and the Rare Disease Data and Technology Coordinating Center.
  • Build a vasculitis clinical specimen bank for storage of serum, plasma, DNA and tissue samples linked to the clinical data repository.
  • Enact a national recruitment program in cooperation with various vasculitis patient advocacy groups.
  • Utilize the extensive resources of the General Clinical Research Centers at each Primary Consortium Site

Aim 2, Conduct a series of related longitudinal studies of novel biomarkers of vasculitis disease activity. Utilizing the consortium Clinical Data Repository and Clinical Specimen Bank and in coordination with biostatistical support from the Data and Technology Coordinating Center, the Consortium Biomarkers Project will use several promising techniques to develop new markers of disease activity including:

  • Proteomics
  • Molecular Markers of Oxidative Stress and Inflammation.
  • Additionally, this program will be established in a fashion that would easily allow for testing of future novel biomarkers by investigators both within and beyond the consortium.

Aim 3, Utilize the consortium and patient base to conduct Phase I and II clinical trials within the proposed grant period and create the infrastructure to greatly facilitate the design and performance of other future trials.

Aim 4, Establish the Vasculitis Clinical Investigator Fellowship as a core mission on the consortium to provide a mechanism to support, train, and mentor fellows interested in establishing academic careers focused on vasculitis research. This aim will address the pressing need in academic medicine for the training and retaining of patient oriented clinical investigators.

Aim 5, Build and contribute to an electronic website resource with substantive content for clinicians, researchers, and patients.

Performance Sites:
Boston University Medical Center, Boston, MA
Cleveland Clinic Foundation, Cleveland, OH
Johns Hopkins University, Baltimore, MD
Mayo Clinic, Rochester, MN

Secondary Sites:
National Cancer Institute, NCI/FDA Clinical Proteomics Program, Bethesda, MD
University Health Network, Mount Sinai Hospital, Toronto University, ON, Canada
Rheumaklinik Bad Bramstedt, Germany
Assistance Hôpitaux Publique De Paris, Hôpital Avicenne, Paris, France
University of Alabama at Birmingham, AL
New York Bone & Joint Beth Israel Medical Center, New York, NY

Patient Support Organizations:

Wegener's Granulomatosis Association (WGA)
Takayasu's Arteritis Research Association (TARA)
Takayasu's Arteritis Foundation International
Churg-Strauss Syndrome International Support Group
The Polyarteritis Nodosa Research and Support Network
International Rett Syndrome Association (IRSA)


Title of Project:

Principal Investigator/
Project Director:

Contact Information:

Patient Inquiries:
Rare Genetic Steroid Disorders Consortium

New, Maria I, M.D.

Mount Sinai School of Medicine
1 Gustave L. Levy Place
Box 1198
New York, NY 10029-6574

Description from the Grant Application:
A consortium of investigators, institutions, and patient support groups will constitute a Rare Disease Clinical Research Consortium focused on a diverse group of disorders characterized by defects in steroidogenesis. We will study the longitudinal history of these rare disorders and determine the outcome of treatment on height, fertility and gender. Long-standing informal collaboration between investigators at Mount Sinai School of Medicine, Rockefeller University, Columbia University, the University of Texas Southwestern Medical Center, the University of Québec, Hospital Debrosses (Lyons), and the Hospital das Clínicas da FMUSP (São Paulo) will facilitate the creation of a productive cooperative research network that draws on the extensive experience of each investigator. Clinical Research Centers at Mount Sinai, Rockefeller, and the University of Texas Southwestern Medical Center will participate. Each investigator in the consortium has followed a large group of patients with a specific genetic defect affecting steroid synthesis over many years, encompassing the natural history of these diseases from prenatal life to death. Creation of a storage and management database will constitute a scaffold for ongoing research, enabling the preservation and use of this large body of clinical data assembled by experts in each disorder. Moreover, design of templates for a standardized clinical description of these disorders will permit prospective studies which can offer open enrollment to affected individuals or individuals at risk. Our research group includes the investigators who have identified the molecular genetic defect for each disorder, where known, and who maintain laboratories dedicated to the identification of new mutations. The combination of clinical and molecular genetic information will raise the standard of medical care and may permit development of novel treatments based on detailed knowledge of the natural history and molecular genetic basis of these disorders. Important elements of our plan are to

  1. Establish the clinical research consortium which pools data from our sites in cooperation with the DTCC and analyzes this data,
  2. Educate young investigators in the management and clinical research of steroid disorders, and
  3. Strengthen our connections with patient support groups to enable individuals affected or at risk to have new kinds of input and access to optimal medical care.

Performance Sites:
Mount Sinai School of Medicine, New York, NY
Rockefeller University, New York, NY
Laval University, Quèbec, Canada
University of Texas Southwestern Medical Center at Dallas, TX
Hospital Debrosses Lyon, France
Hospital das Clinicas da FMUSP, São Paulo, Brazil
Columbia University College of Physicians & Surgeons, New York State Psychiatric Institute, New York, NY

Patient Support Organization:
CARES (Congenital Adrenal Hyperplasia Research, Education, & Support), Foundation, Inc.
National Adrenal Diseases Foundation (NADF)
Androgen Insensitivity Support Group (AISSG)
The Magic Foundation


Title of Project:
Principal Investigator/Project Director:
Contact Information:

Rare Lung Diseases Consortium

Trapnell, Bruce C, M.D.
Division of Pulmonary Biology Children's Hospital Medical Center 3333 Burnet Avenue Cincinnati, OH 45229-3039

Description from the Grant Application:
We seek to establish a research consortium that will facilitate clinical research in rare lung diseases by

  1. Promoting collaboration among centers already focused to clinical research on rare lung diseases,
  2. Attracting & training highly qualified investigators,
  3. Collecting clinical data from geographically distributed patients into a large, centralized database, and
  4. Making the accumulated clinical data available to those affected or possibly affected by a rare lung disease, their clinicians, clinical and basic investigators, and the general public.
Disorders chosen for the initial focus of this network include: Alpha-1 antitrypsin deficiency (AATD), lymphangioleiomyomatosis (LAM), pulmonary alveolar proteinosis (PAP) and hereditary idiopathic pulmonary fibrosis (hIPF). The consortium consists of clinical centers in Ohio (the coordinating center), Colorado, Florida, Maryland, Massachusetts, Oregon, South Carolina and Texas, as well as in Japan and Australia. Centers are required to have and maintain an exemplary record of active clinical research and an adequate rare lung disease patient base. Participating patient support groups include the Alpha-1 Foundation, LAM Foundation and the Pulmonary Fibrosis Foundation. Many of these centers already work together closely and these centers and Foundations are also already closely integrated. For example, the Scientific Directors of all three participating foundations are active clinical investigators at clinical sites within the consortium. Furthermore, clinical sites were chosen from three currently active networks of collaborating clinical centers that include more than 50 sites in 24 states distributed throughout the United States. All participating domestic clinical sites are associated with an active, NIH-supported general clinical research center (GCRC). Each center provides components required of the proposed consortium including ongoing longitudinal clinical studies, an excellent clinical training program, and an active clinical research trials program designed to test novel therapies, and develop diagnostic tests or evaluate outcome measures for rare lung diseases. Each of the Foundations provides education for patients, the lay public, and the medical community. Importantly, one consequence has been already the formation of the "Rare Lung Disease Foundation Consortium," which permits patient support groups with a greater infrastructure to "nurture" the growth of less well-developed groups. It also provides support for individuals affected by a rare lung disease for which there is currently no foundation. Ongoing clinical, basic, and translational studies at the centers chosen have already yielded critical insights into molecular mechanisms underlying lung function and defense in health and disease.

Performance Sites:
Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH
Cleveland Clinic Foundation, Cleveland, OH
Oregon Health & Sciences University, Portland, OR
International Medical Center of Japan, Tokyo, Japan
Harvard University and Brigham and Women's Hospital, Boston, MA
Medical University of South Carolina, Charleston, SC
National Heart, Lung, and Blood Institute, Bethesda, MD
National Jewish Medical and Research Center (NJMRC), Denver, CO
Royal Melbourne Hospital, Melbourne, Australia
University of Florida Medical Center, Gainesville, FL
University of Texas Health Center, Tyler, TX

Patient Support Organizations:
Alpha-1 Foundation
The LAM Foundation
Pulmonary Fibrosis Foundation


Title of Project:

Principal Investigator/Project Director:
Contact Information:

Rare Thrombotic Diseases Consortium

Ortel, Thomas L, M.D., Ph.D.
Department of Medicine, School of Medicine,
Duke University
0563 Stead Building
Box 3422 Medical Center
Durham, NC 27710

Description from the Grant Application:

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

1) 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 ‘thromobotic storm.'
  • Identify risk factors for thrombosis in patients with antiphospholipid antibodies and HIT.
  • Define the natural history of patients with elevated heparin-platelet factor 4 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.
2) 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.
3) 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.

Performance Sites:

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
Centers for Disease Control and Prevention, Atlanta, GA

Patient Support Organizations:

Platelet Disorder (PD) Support Association
FVL (Factor V Leiden) Thrombophilia Awareness Project


Title of Project:

Principal Investigator/Project Director:
Contact Information:



Genetic Disorders of Mucociliary Clearance Consortium

Knowles, Michael R., MDCF/Pulmonary
Research and Treatment Center
7019 Thurston-Bowles Building, CB#7248
The University of North Carolina at Chapel Hill
3333 Burnet Avenue Chapel Hill, NC 27599-7248

Description from the Grant Application:
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 two central hypotheses are that

  1. 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

  2. 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 five-year longitudinal study of 300 patients with PCD, we will use innovative techniques, including measurement of PFTs and HRCTs 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 evaluate novel therapeutic agents. The existing training program in rare airway diseases will be extended to established and young investigators at UNC, and to investigators at other sites. 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.
Performance Sites:
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

Patient Support Organization:
Primary Ciliary Dyskinesia (PCD) Foundation
Cystic Fibrosis Foundation (CFF)


Title of Project:

Principal Investigator/Project Director:

Contact Information:

Rare Liver Diseases Consortium

Sokol, Ronald J., M.D.

Children’s Hospital, Department of Pediatrics, 1056
E 19th Avenue, B290
Denver, CO 80218

Description from the Grant Application:
The Principal and Co-Investigators propose 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 five clinical sites within the United States, each with investigators who have extensive clinical experience, patient populations, and research programs for these disorders, and each with a General Clinical Research Center (GCRC). The consortium will focus on investigations of 5 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 a-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

  • 3 biological core facilities to ensure the highest quality analysis of genetic information, liver histopathology, and bile acid biochemistry for subjects enrolled in this study;
  • an administrative core;
  • 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.

Performance Site:
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
University of Colorado Health Sciences Center, Denver, CO

Patient Support Organizations:
American Liver Foundation
The Alagille Syndrome Alliance
Alpha-1 Foundation
Children’s Liver Association for Support Services (CLASS)
United Mitochondrial Disease Foundation (UMDF)


Title of Project:

Principal Investigator/Project Director:

Contact Information:

Rare Diseases Data and Technology Coordinating Center

Krischer, Jeffrey P, Ph.D.

H. Lee Moffitt Cancer Center and Research Institute
12902 Magnolia Drive
Tampa, FL 33612

Description from the Grant Application:
This proposal seeks support to establish a Data and Technology Coordinating Center (DTCC) for the Rare Diseases Clinical Research Network. The DTCC will play an active role in the development of the Network. It will facilitate research in the design of clinical protocols and the data management and analysis necessary to support them. Working with the Rare Diseases Clinical Research Consortia, the DTCC will make available a coordinated clinical data management system for the collection, storage and analysis of data from multiple diseases and multiple clinical sites. The data management system will be a secure web-based system that includes the capability to capture and integrate many different forms of data (clinical, imaging, genetics, pathology, etc.), and the scalability to serve as a national clinical information network. Among its features will be a user-friendly system for recruitment and referral, tools for cross-disease data mining, data sharing, and a public portal to relevant data resources. This application applies novel approaches to and technologies for data management and training, includes the use of web-based video streaming and also seeks to conduct research and development of new approaches to distributed computing, federated databases, and data mining.

Performance Site:
H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL

Supplementary Grant Program

In FY 2002, the ORD provided one-time supplementary awards to 44 existing intramural and extramural Institute and Center research grants. The purpose of these supplements was to generate pilot and demonstration projects as well as research training foci on rare diseases and planning grants for a subsequent Request for Applications (RFA) for rare diseases research. The supplemental grants ranged from research on prion disease to scleroderma, to congenital heart block, to the molecular basis for neuronal migration, elctrocorticographic studies of human cortical function, and the study of marrow stromal cells for lysosomal disease CNS defects.

For more information, please contact:

Giovanna M. Spinella, M.D.
CDR, US Public Health Service
Director, Extramural Research Program
Office of Rare Diseases, OD, NIH
6100 Executive Blvd. Rm. 3B01-MSC 7518
Bethesda, MD 20892-7518
Telephone: 301 402-4336
Fax: 301 480-9655
E-mail: ord@od.nih.gov

Last Reviewed: August 10, 2004

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