Table of Contents
- Overview: NDSI-IEM Program Description
- A brief description of NDSI-IEM’s goals, collaborators, and program components.
- Inborn Errors of Metabolism (IEM): What they are and why more research is needed on the nutritional interventions that are used.
- Mission and Guiding Principles
- NDSI-IEM mission statement and guiding principles.
- Meetings, Workshops, and Other Activities
- Links to meetings, workshops, and other relevant collaborative efforts.
- Resources for Researchers
- Links to Web sites of federal agencies that contain useful resources for researchers.
In October 2010, the NDSI-IEM program was launched in the Office of Dietary Supplements (ODS) to explore the research evidence supporting the use of nutrition and dietary supplement interventions for inborn errors of metabolism (IEM) and the infrastructure needed to carry out new research. In collaboration with the
Office of Rare Diseases Research (ORDR), and with input from a broad range of interested and involved parties, challenges and barriers to conducting research on nutritional treatments for IEM are being identified. Strategies will be developed to support evidence-based research on the safety and effectiveness of nutritional management modalities in IEM.
Nutrition and dietary supplement interventions are the main management strategies for a number of IEM. Many IEM are identified through newborn screening, a successful public health program that screens virtually all newborns in the United States within the first 48 hours of birth (Newborn Screening: The Facts and Discretionary Advisory Committee on Heritable Disorders in Newborns and Children). Early identification and treatment of an IEM reduces the medical and developmental problems associated with these conditions. The inherited genetic mutation(s) in each IEM prevent the body from breaking down substances contained in the diet. Infants with these conditions are generally healthy at birth. Symptoms begin to appear when they are exposed to breast milk or infant formula containing dietary components that their bodies cannot use properly. As a result, compounds build up in the blood and brain, leading to undesired health outcomes. These conditions are managed by restricting the offending dietary components and providing nutrients that become deficient due to the limited diet.
Over the past 50 years, technological advances and public demand have led to an increase in the number of conditions screened in the newborn period from one (phenylketonuria, PKU) to over 50 different conditions in some states. Although individuals identified with IEM in infancy are now living into adulthood, the nutritional management that promotes proper growth and development and maintains long-term health for these individuals is not known for many of the conditions.
Additionally, IEM are rare diseases and the nutrition and dietary supplement interventions are regulated as foods, not as drugs. These factors have contributed to the difficulties in conducting research on these management strategies.
Mission and Guiding Principles
Mission: To identify gaps in understanding the safety and effectiveness of nutrition and dietary supplement interventions used to treat individuals with IEM. Through collaboration and partnerships with a wide range of interested parties, this program will develop and implement a plan to conduct evidence-based research to eliminate these gaps.
- To serve individuals from birth into old age.
- To partner and collaborate with involved and interested parties.
- To harmonize research-related activities across public and private groups.
- To educate those who have an impact on the well-being of persons with IEM.
- To think creatively and consider new approaches to solving problems.
Meetings, Workshops, and Other Activities
In January 2011, federal partners confirmed the need for the NDSI-IEM initiative. As a result, a workshop was held in late 2011 to engage the wider metabolic community and develop a plan to promote evidence-based research of nutrition and dietary supplement interventions used in IEM. Participants represented advocacy and patient organizations; professional associations; companies that make medical foods, prescription drugs, and other nutritional products used in the management of IEM; the Health Resources and Services Administration’s Regional Genetic and Newborn Screening Services Collaboratives; agencies, institutes, and centers within the Department of Health and Human Services; and the metabolic clinical, research, and academic communities.
- The 2011 workshop led to the development of several important ongoing activities and a paper:
- Two professional associations (Society for Inherited Metabolic Disorders [SIMD] and Genetic Metabolic Dietitians International [GMDI]) have conducted a survey of the metabolic community regarding the effectiveness of nutrition and dietary supplement treatments for IEM. Results will be forthcoming and will be made available via the organizations’ Web sites.
- Expanding Research to Provide an Evidence Base for Nutritional Interventions for the Management of Inborn Errors of Metabolism
August 5, 2013
Camp KM, Lloyd-Puryear MA, Yao L, Groft SC, Parisi MA, Mulberg A, Gopal-Srivastava R, Cederbaum S, Enns GM, Ershow AG, Frazier DM, Gohagan J, Harding C, Howell RR, Regan K, Stacpoole PW, Venditti C, Vockley J, Watson M, Coates PM. Mol Genet Metab. 2013;97:1235-42.
- Posters and presentations on the NDSI-IEM:
- Posters were presented at SIMD’s annual meetings in 2011 and 2012.
- Updates on NDSI-IEM activities were presented to the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children in February and May, 2012.
- Poster and platform presentation on NIH activities related to IEM were presented at the National Organization of Rare Disorders annual meeting on October 22, 2012.
- Poster was presented at the American College of Medical Genetics annual meeting in March, 2013.
- Support of IEM guideline development.
- Medical foods-related paper:
Resources for Researchers
- National Institutes of Health (NIH)
- Extramural research grants are awarded to investigators throughout the United States and abroad. Approximately 10 percent of the NIH budget supports intramural investigators, NIH staff who conduct research.
- NIH Institutes and Centers (ICs)
- NIH is made up of 27 ICs, each with a specific research agenda, often focusing on particular diseases or body systems.
- Office of Extramural Research (OER)
- OER provides leadership, oversight, tools, and guidance to administer and manage NIH grants policies and operations. OER serves as a link between the NIH and the biomedical research community by guiding investigators through the process of obtaining grant funding.
- Funding Opportunities and Notices
- OER (above) maintains a listing of active Requests for Applications (RFAs) and Program Announcements (PAs). The Web site includes links to related resources.
- Center for Scientific Review (CSR)
- CSR serves as the central receipt point for most federal grant applications submitted to NIH. CSR assigns the grant application to an NIH Institute and to a Scientific Review Group, also known as a Study Section.
- Solicited Grant Applications
- This resource lists all active RFAs with the ability to browse or search by topic area.
- Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER)
- This tool allows users to search a repository of NIH-funded research projects. The information found in RePORTER is drawn from several current databases: eRA [Electronic research administration] databases;
PubMed Central; the NIH Intramural Database (NIDB); and iEdison.
- NIH Grant Writing Tips Sheets
- This resource includes information on choosing an appropriate NIH funding mechanism, peer review guidelines and information, and advice on preparing grant applications.
- National Center for Complementary and Alternative Medicine (NCCAM) Tips for New NIH Research Grants Applicants
- This Web site provides tips on grant writing for NIH research applicants.
- Glossary of Funding and Policy Terms and Acronyms
- This Web site provides a glossary to help research applicants with the NIH application process.
- The NIH Clinical Center’s Web site
- The Clinical Center’s Web site provides details on ongoing NIH clinical trials. At this time, use of the Clinical Center is restricted to NIH staff who conduct research and their collaborators. However, NIH may open the Clinical Center to external researchers in the future.
- Common Fund Regulatory Science Program
- This program fosters development, availability, and evaluation of new or improved ways to understand and improve product safety, quality, effectiveness, and manufacturing throughout the life-cycle of a product.
National Institutes of Health—Rare Diseases
- National Center for Advancing Translational Sciences (NCATS)
- NCATS develops new technology that can be transferred through collaborations and licenses to others for further research, development, and commercialization. NCATS strives to develop innovations to reduce, remove or bypass costly and time-consuming barriers in the research process in an effort to speed the delivery of new drugs, diagnostics, and medical devices to patients.
- The Office of Rare Diseases Research (ORDR)
- ORDR is organizationally part of NCATS. The goals of ORDR are to identify, stimulate, coordinate, and support research to respond to the needs of patients who have rare diseases.
- The Rare Diseases Clinical Research Network (RDCRN)
- RDCRN comprises regional centers working to promote clinical research on diagnosis, prevention, control, and treatment methods for rare diseases. The research projects are designed to improve availability of rare disease information, treatment, clinical studies, and general awareness for both patients and the medical community. RDCRN also aims to provide up-to-date information for patients and to assist in connecting patients with advocacy groups, expert doctors, and clinical research opportunities.
Global Rare Diseases Patient Registry and Data Repository (GRDR)
- GRDR provides the rare disease community a resource of collective standardized patient information (unidentifiable), to accelerate research and advance therapeutic development.
- Rare Disease-HUB (RD-HUB) of the Office of Rare Diseases Research (ORDR)
- This Web site contains a searchable database of biological specimens collected, stored, and distributed by biorepositories in the United States and around the globe.
- Genetic and Rare Diseases Information Center (GARD)
- This Center was established to provide access to information specialists who supply current and accurate information about genetic and rare diseases in both English and Spanish.
- Common Fund Undiagnosed Diseases Program (UDP)
- UDP promotes the use of genomic data in disease diagnosis and engages basic researchers to define clearly the mechanisms underlying the diseases so that treatments may be identified.
- Therapeutics for Rare and Neglected Diseases
- TRND builds collaborations with NIH, FDA, academic scientists, nonprofit organizations, and pharmaceutical and biotechnology companies to speed development of new therapies.
- Cures Acceleration Network (CAN)
- CAN was established to stimulate the development of high need cures for debilitating and life threatening diseases by reducing the number of barriers that investigators face between the time of basic research discoveries and initiation of clinical trials.
- Bridging Interventional Development Gaps (BrIDG)
- BrIDG provides successful applicants developing therapeutic agents with access to critical resources in support of preclinical studies.
- Discovering New Therapeutic Uses for Existing Molecules
- This initiative is a collaborative pilot program of NCATS designed to develop partnerships between pharmaceutical companies and the biomedical research community to advance therapeutic development.
- Tissue Chip for Drug Screening
- This initiative represents an interagency collaboration with Defense Advanced Research Projects Agency (DARPA) and NCATS.
Food and Drug Administration
- FDA Office of Orphan Products Development (OOPD)
- OOPD’s mission is to advance the evaluation and development of products (drugs, biologics, devices, or medical foods) that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions.
- The Orphan Drug Act (ODA)
- Through the ODA, FDA grants special status to a product to treat a rare disease or condition upon request of a sponsor. A marketing application for such a product is not subject to a prescription drug user fee unless the application includes an indication for other than a rare disease or condition.
- Humanitarian Use Device (HUD) program
- HUD was established in 1990 with passage of the Safe Medical Devices Act and creates an alternative pathway for getting market approval for medical devices that may help people with rare diseases or conditions.
- The Orphan Products Grants Program
- The goal of this program is to encourage clinical development of products for use in rare diseases or conditions. The products studied can be drugs, biologics, medical devices, or medical foods.
- FDA Pediatric Device Consortia Grant Program
- The goal of this program is to support the development of nonprofit partnership designed to stimulate projects that will promote pediatric device development.