The RDCRN is designed to advance medical research on rare diseases by providing support for clinical studies and facilitating collaboration, study enrollment and data sharing.
Currently, the RDCRN consists of 22 distinct clinical research consortia and a Data Management and Coordinating Center (DMCC). Each consortium focuses on at least three related rare diseases, participates in multisite studies and actively involves patient advocacy groups as research partners. The DMCC enables uniform high-quality data collection and analysis and facilitates information sharing across the network. This robust data source helps scientists better understand the common elements of rare diseases so they may apply that knowledge to improving diagnosis and treatment for these conditions.
On Oct. 8, 2014, NIH announced awards to expand the RDCRN. Descriptions of the 2014 consortia and DMCC follow:
- Autonomic Rare Diseases Clinical Research Consortium
- Brain Vascular Malformation Consortium: Predictors of Clinical Course
- Brittle Bone Disorders Consortium of the Rare Diseases Clinical Research Network
- Chronic Graft Versus Host Disease Consortium
- Clinical Research in Amyotrophic Lateral Sclerosis and Related Disorders for Therapeutic Development
- Consortium of Eosinophilic Gastrointestinal Disease Researchers
- Developmental Synaptopathies Associated with TSC, PTEN and SHANK3 Mutations
- Dystonia Coalition
- Frontotemporal Lobar Degeneration Clinical Research Consortium
- Genetic Disorders of Mucociliary Clearance Consortium
- Inherited Neuropathies Consortium
- Lysosomal Disease Network
- Nephrolithiasis and Kidney Failure: The Rare Kidney Stone Consortium
- Nephrotic Syndrome Rare Disease Clinical Research Network
- North American Mitochondrial Disease Consortium
- Porphyrias Consortium
- Primary Immune Deficiency Treatment Consortium
- Rare Lung Diseases Consortium: Molecular Pathway-Driven Diagnostics and Therapeutics for Rare Lung Diseases
- Rett Syndrome, MECP2 Duplications and Rett-Related Disorders Natural History
- Sterol and Isoprenoid Research Consortium
- Urea Cycle Disorders Consortium
- Vasculitis Clinical Research Consortium
- RDCRN Data Management and Coordinating Center
David Robertson, M.D.
Vanderbilt University, Nashville, Tennessee
Multiple system atrophy, pure autonomic failure and Lewy body dementia cause problems in the brain, heart, blood vessels, stomach, bowel and bladder. These disorders lead to severe neurological disabilities and, in some cases, death. The Autonomic Rare Diseases Clinical Research Consortium (RDCRC), which includes physicians and scientists from Vanderbilt University, Mayo Clinic, Beth Israel Deaconess Medical Center/Harvard University, New York University, NIH and other collaborators, works to improve understanding of autonomic diseases and their causes. During the past five years, the Autonomic RDCRC, with support from the MSA Coalition and other patient advocacy groups, carried out drug trials and created a website that educates patients, doctors and researchers about these conditions. As the Autonomic RDCRC scales up natural history studies, the investigators aim to learn from patients and improve ways to treat these diseases.
Michael T. Lawton, M.D.
University of California, San Francisco
The Brain Vascular Malformation Consortium (BVMC) focuses on three rare brain conditions: cerebral cavernous malformation, Sturge-Weber syndrome and hereditary hemorrhagic telangiectasia. These disorders are poorly understood and costly to manage, and they can cause serious complications such as hemorrhage; seizures; and problems with spinal cord, nerve or brain function. In its first few years, BVMC made great progress in creating patient registries and searching for magnetic resonance imaging, genetic and chemical markers for these diseases, which would help doctors diagnose and treat patients. Specific aims of BVMC include continuing these two important lines of work and developing future clinical studies on and therapeutics for these disorders.
Brendan Lee, M.D., Ph.D.
Baylor College of Medicine, Houston
Brittle bone disorders (BBDs), also known as osteogenesis imperfecta, include 13 inherited conditions involving fragile bones that break easily. BBDs can cause deformity, chronic pain and death. This project’s goal is to form a BBD Rare Disease Clinical Research Consortium, composed of eight medical research sites, to better understand and treat BBDs. The consortium aims to explore the genetics of BBDs, observe the natural history of bone fractures in several types of BBDs, test new treatments, develop new techniques for studying BBD causes and evaluating severity, and optimize a symptom-reporting tool for adults with BBDs. The Osteogenesis Imperfecta Foundation will coordinate junior scientist research training.
Stephanie J. Lee, M.D., M.P.H.
Fred Hutchinson Cancer Research Center, Seattle
After a blood or bone marrow transplant, the donor’s immune system may see the host’s body as foreign and attack it, causing a condition called graft versus host disease (GVHD). Immune-mediated disorders (IMDs), including late acute and chronic GVHD, develop in up to 70 percent of transplant recipients. Chronic GVHD can cause severe illness and is the leading cause of non-relapse-related death more than two years after a transplant. For this project, this Rare Diseases Clinical Research Consortium will continue research to advance the understanding and treatment of IMDs. Aims include continuing clinical studies on new treatments for various forms of late acute and chronic GVHD; conducting a long-term observational study of patients with IMDs; exploring the clinical and biological factors that increase risk for GVHD; collaborating with three patient advocacy organizations; and training, education, outreach and cooperation with other members of the RDCRN.
Clinical Research in Amyotrophic Lateral Sclerosis and Related Disorders for Therapeutic Development
Michael Benatar, MD., Ph.D.
University of Miami Miller School of Medicine, Florida
Amyotrophic lateral sclerosis (ALS) is a fatal disease that involves progressive death of motor nerves in the brain, brainstem and spinal cord. The disease is closely related to disorders such as primary lateral sclerosis, hereditary spastic paraplegia, progressive muscular atrophy and frontotemporal dementia. These diseases have shared genetic causes and underlying biology. They also have in common a lack of effective therapies. The Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium brings together a multidisciplinary group of researchers and a diverse array of patient advocacy groups to bridge the gap between basic scientists and investigators engaged in applied clinical research. The goals of the CReATe Consortium are to advance understanding of the contribution of genetics to these complex disorders, promote development of biological features (biomarkers) that may enhance therapeutic development efforts, train a new generation of clinical scientists, and engage the public and scientific communities in partnerships that enhance clinical research and therapy development.
Marc E. Rothenberg, M.D., Ph.D.
Cincinnati Children’s Hospital Medical Center
Eosinophilic esophagitis, eosinophilic gastritis and eosinophilic colitis are disorders in which immune cells (called eosinophils) build up in the digestive tract, causing tissue damage to the esophagus, stomach or colon. These disorders are painful and lifelong, and they make it hard or impossible for people to eat many or all foods. This project aims to form a clinical research network called the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) that will include clinical centers in California, Colorado, Illinois, Indiana, Maryland, Massachusetts, North Carolina, Ohio, Pennsylvania and Switzerland. CEGIR’s goals are to collect and store clinical information and biological samples from patients to better understand, diagnose and treat these conditions; develop the best methods to measure symptoms and track patients; develop better treatments; make data available to patients, clinicians, researchers and the public; and engage and cooperate with patient advocacy groups.
Mustafa Sahin, M.D., Ph.D.
Boston Children’s Hospital
Autism spectrum disorder (ASD) and intellectual disability (ID) are related disorders that involve delayed or impaired social, communication and mental skills. This project will explore three genetic syndromes caused by mutations in three genes (TSC1/2, PTEN and SHANK3) that have been linked to ASD and ID. These syndromes have shared genetic pathways, suggesting that they could be treated with similar approaches. Studies will characterize the physiological and clinical features of children with the three syndromes, use imaging to identify biological features (biomarkers) indicating the presence and severity of the disorders, and create a storage bank for tissue and blood samples to further explore the genetic bases of these syndromes. Additionally, a clinical trial using an mTOR inhibitor, previously studied in TSC mutations, will be performed for individuals with PTEN mutations.
Hyder A. Jinnah, M.D., Ph.D.
Emory University, Atlanta
Dystonia syndromes are disorders that cause uncontrollable, repetitive shaking, turning and twisting of affected body parts. The most common dystonia disorders affect the head and neck, eyelids, vocal cords, hands and forearms, and sometimes the entire body. The overall goal of the Dystonia Coalition is to hasten progress in dystonia research. Specific aims include understanding the natural history of dystonia syndromes, crafting formal diagnostic guidelines for these syndromes, creating a bank of DNA samples for dystonia research, and developing a standardized way to measure the severity of the disorder.
Adam L. Boxer, M.D., Ph.D.
University of California, San Francisco
Frontotemporal lobar degeneration (FTLD) is the general term for a group of rare, fatal brain diseases that cause thinking and movement problems and currently have no effective treatments. The purpose of this project is to build an FTLD clinical research consortium (CRC) to support the development of FTLD therapies and conduct clinical trials. The FTLD CRC will be headquartered at the University of California, San Francisco; will comprise 14 medical research centers; and will partner with six patient advocacy groups. The consortium aims to prepare for clinical trials of new therapies by investigating the underlying biology of FTLD, characterizing the clinical characteristics of FTLD patients and individuals with elevated genetic risk, piloting new brain imaging techniques to better understand FTLD, and training researchers in therapeutic development.
Michael R. Knowles, M.D.
University of North Carolina at Chapel Hill
The Genetic Disorders of Mucociliary Clearance Consortium comprises a group of research clinics studying rare lung diseases that can cause chronic airway infections and damage to the lungs. In the past five years, the consortium has created a noninvasive test for these disorders and helped identify the genetic mutations that can cause these conditions. Goals for the future include earlier diagnosis, improved patient care and more effective treatments for rare lung diseases. The consortium has five specific aims: to carry out four clinical research projects to better understand these diseases; to start a program to create and improve diagnostic tests; to train new physicians and scientists in rare diseases research and help these investigators advance in their careers; to team up with patient advocacy groups to provide educational websites, symposia and lectures; and to improve the peer-review process for related scientific studies.
Michael E. Shy, M.D.
University of Iowa, Iowa City
Charcot-Marie-Tooth disease (CMT) is a neuropathy, or disorder of the nervous system. The Inherited Neuropathies Consortium (INC) is a network of researchers working to find the best treatments for CMT. Over the past few years, the INC has carried out studies; begun testing possible markers for CMT; enrolled thousands of patients in its studies; trained young scientists in CMT research; and created a website that provides information about CMT to patients, families and researchers. INC’s future goals include conducting further studies and more clinical trials; continuing the search for biological features (biomarkers) of disease; and maintaining and updating its website to continue providing information to patients, their families, doctors and researchers.
Chester B. Whitley, M.D., Ph.D.
University of Minnesota, Minneapolis
The rare conditions known as lysosomal diseases affect 1 in 3,000 people and can cause severe illness and disability. In lysosomal diseases, chemicals build up in the body’s cells. This buildup kills the cells, which can lead to death of the patient. The Lysosomal Disease Network brings together doctors, researchers and patient advocacy groups to solve major challenges in diagnosis, disease management and treatment for these diseases. Plans for the next five years include conducting 14 research projects; funding two research fellows each year; hosting an annual “WORLD Symposium” scientific meeting; presenting a “Lysosomes 101” course for experts; and continuing global communication through a listserv, webinars and the network’s website.
Dawn S. Milliner, M.D.
Mayo Clinic, Rochester, Minnesota
Severe, inherited forms of nephrolithiasis, or kidney stones, involve repeated stone formation, kidney damage, and an increased risk for chronic kidney disease and loss of kidney function. The Rare Kidney Stone Consortium (RKSC) formed five years ago to advance understanding and treatment of these disorders. This project will build on RKSC’s previous progress. Its goals are to engage and involve patients and patient advocacy groups as research partners, identify patients at risk for loss of kidney function, study mechanisms and causes of kidney injury, and identify targets for potential treatment studies. RKSC also will maintain a registry of patient clinical information and a biobank for storing patients’ urine and blood samples for use in studies.
Matthias Kretzler, M.D.
University of Michigan, Ann Arbor
Nephrotic syndrome (NS) is a group of rare renal diseases with serious complications. The diseases that define NS are focal and segmental glomerulosclerosis, minimal change disease and membranous nephropathy. Despite their rarity, these glomerular diseases generate enormous individual, economic and societal burdens. Some types of the syndrome are hereditary, but other types, for reasons largely unknown, can develop later in life. The Nephrotic Syndrome Study Network (known as NEPTUNE) brings together physician scientists at 23 sites in the United States and Canada, along with patient advocacy groups to advance research on the diseases that define NS. Already, NEPTUNE has collected biological material and detailed clinical data from more than 450 NS research participants, and has supported pilot and ancillary studies utilizing the NEPTUNE data resources. Using a systems biology approach, NEPTUNE aims to leverage its resources to define NS in functional terms and to develop and test novel treatments.
Michio Hirano, M.D.
Columbia University, New York
Mitochondrial diseases affect approximately 1 in every 5,000 people. These diseases can cause muscle weakness, difficulty thinking, seizures, hearing and vision loss, stomach problems, learning disabilities, and organ failure. The North American Mitochondrial Disease Consortium (NAMDC) is a network of clinicians and researchers at 17 different clinical sites working to better understand mitochondrial diseases, improve diagnosis and explore treatments. In the past few years, NAMDC has established a biorepository for tissue samples, a large registry and follow-up study with more than 660 patients, a website to educate and recruit patients, and diagnostic criteria for mitochondrial diseases. NAMDC also has initiated research studies that focus on several subtypes of mitochondrial diseases as well as a training program to educate the next generation of researchers. During the next few years, NAMDC will expand its clinical study and biorepository, refine diagnostic criteria, begin new studies of possible treatments, and continue training clinician-scientists.
Robert J. Desnick, Ph.D., M.D.
Icahn School of Medicine at Mount Sinai, New York
The porphyrias are a group of rare, inherited disorders caused by problems with one of eight enzymes necessary for the production of heme, an important component of hemoglobin and other proteins. The porphyrias are classified as either acute hepatic or cutaneous; the former are characterized by acute attacks of severe abdominal pain accompanied by nausea, vomiting and other symptoms, whereas the latter have various symptoms, including blistering or burning in response to sun exposure. The rarity of these diseases has limited understanding of how they naturally progress and what other factors influence them. The Porphyrias Consortium brings together porphyria experts at six academic institutions, the American Porphyria Foundation and biopharmaceutical companies interested in improving diagnosis or developing new treatments for these diverse diseases. The consortium aims to continue studying the causes, characteristics and genetics of the porphyrias; improve methods of diagnosis; develop and test new treatments; and train the next generation of porphyria clinicians and researchers.
Morton J. Cowan, M.D.
University of California, San Francisco
Primary immune deficiencies (PIDs) are inherited defects of the immune system that cause patients to develop repeated, often severe and life-threatening infections. The Primary Immune Deficiency Treatment Consortium (PIDTC) formed in 2009 to develop treatments for children affected with three types of PIDs: severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome and chronic granulomatous disease. PIDTC includes five patient advocacy groups and 43 medical research centers in North America alongside three centers in Europe. The project’s goals are to follow the long-term health outcomes of patients who have received standard treatments, including hematopoietic cell transplantation (HCT), gene therapy and enzyme replacement therapy; identify biological features (biomarkers) that predict presence of disease and treatment response; define the underlying biology of HCT in SCID patients; find optimal doses of chemotherapy for HCT; promote newborn screening for SCID; train junior scientists in PID clinical research; and engage patient advocacy groups and share information about PIDs with families, scientists and clinicians.
Rare Lung Diseases Consortium: Molecular Pathway-Driven Diagnostics and Therapeutics for Rare Lung Diseases
Bruce Trapnell, M.D.
Cincinnati Children’s Hospital Medical Center
The goal of this project is to form a Rare Lung Diseases Clinical Research Consortium (RLDC) that focuses on better understanding and treating three rare lung diseases: lymphangioleiomyomatosis, pulmonary alveolar proteinosis and Hermansky-Pudlak syndrome. RLDC will include medical research centers and four patient support groups. It will aim to better understand rare lung diseases by following patients over time; conducting treatment studies; developing new methods to diagnose, treat and measure health outcomes in rare lung disease patients; providing clinical research training to young scientists; and developing rare lung disease educational materials for patients, medical providers and the public.
Alan K. Percy, M.D.
University of Alabama at Birmingham
This project involves clinical research into three disorders of the nervous system: Rett syndrome (RTT), MECP2 duplication disorder and RTT-related disorders. These conditions strike previously healthy-seeming children — usually girls for RTT and boys for MECP2 duplication disorder — early in their lives and can lead to seizures, difficulty with fine motor control and walking, and intellectual disability. The research center’s work takes the form of a natural history study with three major goals: identify and understand the core clinical features of each disorder; identify factors that can modify the severity of the disorders; and understand the relationship between patients’ symptoms and their brain imaging and electroencephalography alterations.
William B. Rizzo, M.D.
University of Nebraska Medical Center, Omaha
The Sterol and Isoprenoid Research Consortium (STAIR) studies a group of rare, inherited metabolic diseases that often go undiagnosed and have puzzling symptoms. Even after diagnosis, the diseases have no effective therapies. The STAIR Consortium will uncover relevant knowledge that can advance the diagnosis and therapeutic options for patients with these rare diseases. The consortium aims to raise awareness, support diagnosis and develop treatments for STAIR diseases; carry out large studies and clinical trials to improve understanding of these conditions; and train the next generation of young physicians and scientists to become leaders in understanding, diagnosing and treating STAIR diseases.
Mark L. Batshaw, M.D.
Children’s National Medical Center, Washington, D.C.
Urea cycle disorders (UCDs) are rare but devastating genetic conditions. A decade ago, the Urea Cycle Disorders Consortium (UCDC) became one of the first members of the RDCRN. Since then, UCDC has flourished into an international network of 14 academic centers in the United States, Canada and Europe that provide state-of-the-art care and conduct cutting-edge clinical research. During the next five years, the consortium will focus research on three major studies as well as pilot studies on innovative diagnostics and therapies. The three major protocols include a long-term natural history study of patients with UCDs that has been active since 2006; a project combining neuroimaging and neuropsychology to learn more about how UCDs affect brain function; and a clinical trial of an innovative treatment to correct an underlying problem for patients with UCDs. The consortium also continues to train the next generation of rare diseases researchers, provide education on UCDs to health care professionals and the public in partnership with the National Urea Cycle Disorders Foundation, and work with the pharmaceutical/biotechnology industry to develop and test novel medications and treatments to help improve the lives of those affected by UCDs.
Peter A. Merkel, M.D., M.P.H.
University of Pennsylvania, Philadelphia
Vasculitis refers to a group of rare diseases that involve inflammation of blood vessels, which disrupts blood flow and often causes damage to the body’s organs. The cause of most forms of vasculitis remains unknown, and treatments involve the use of strong medications that can have serious side effects. The Vasculitis Clinical Research Consortium (VCRC) is an international, multicenter clinical research infrastructure for the study of vasculitis. Established in 2003, VCRC has grown to include 17 academic medical centers in the United States and Canada dedicated to the study of vasculitis. The consortium also partners with more than 50 other centers worldwide for the conduct of clinical trials. For this project, VCRC will continue its efforts to better understand vasculitis by adding new clinical sites, extending study periods and expanding patient enrollment in several ongoing long-term studies of vasculitis. The consortium focuses on conducting clinical trials of new therapies for vasculitis, studying the genetics of the disease, discovering new blood tests to help monitor and understand the disease, conducting online research through the VCRC Patient Contact Registry, and training young scientists in the study of vasculitis. All of these activities involve a strong partnership with patients and advocacy groups.
Jeffrey P. Krischer, Ph.D.
University of South Florida, Tampa
The Data Management and Coordinating Center (DMCC) is the technological backbone of the RDCRN. Over the past few years, the DMCC has created and developed the systems, processes and procedures needed to enroll more than 24,000 participants in 128 studies; built databases and registries; and offered a user-friendly website that provides information on rare diseases and invites patients to join clinical trials. In the future, the DMCC will continue to offer RDCRN researchers a secure and efficient way to store, analyze and manage study data; incorporate new technologies such as genomics; train new researchers; and enroll and educate patients through its website.