In my November 2015 letter, I highlighted NIH and NIAMS investments in pediatric research, including a major new initiative, called Environmental Influences on Child Health Outcomes (ECHO) and a related trans-NIH, NIAMS-led program, the Validation of Pediatric Patient-Reported Outcomes in Chronic Diseases (PEPR) Consortium. In this month’s letter, I share updates on these efforts and other NIAMS pediatric research activities.
In September 2016, the NIH awarded several components of ECHO. This seven-year project seeks to improve understanding of the effects of environmental, societal and behavioral exposures on child health and development from conception through early childhood. ECHO draws on existing pediatric cohorts with a goal of enrolling more than 50,000 children from racially, socioeconomically and geographically diverse backgrounds. As ECHO progresses, it will create a new, larger cohort from the existing ones to extend its reach. The NIAMS provides ongoing input to ECHO on its Patient Reported Outcomes Core and on pediatric cohorts related to NIAMS mission areas.
To support ECHO, the NIAMS-led, trans-NIH PEPR program is validating patient-reported outcome measures for use in clinical research and care for children with a variety of chronic diseases, including diseases within the NIAMS purview, such as atopic dermatitis, juvenile idiopathic arthritis and lupus. Since PEPR’s launch in September 2015, investigators at the four consortium centers have worked to harmonize their efforts. In addition to the individual projects that will be conducted at each center, the group is planning consortium-wide studies. PEPR investigators are working to advance several pediatric patient-reported outcomes to the point of qualification by the U.S. Food and Drug Administration for use in clinical trials of new therapies.
Beyond ECHO and PEPR, the Institute also invests in several large collaborative research efforts that include a focus on children, including:
- The pediatric component of a recently launched trans-NIH program called the Molecular Transducers of Physical Activity Consortium (MoTrPAC). This new initiative, launched by the NIH Common Fund in December 2016, seeks to discover the molecular mechanisms that provide physical activity’s beneficial health effects. The pediatric clinical center, which is one of several NIAMS-led components, will examine the effects of physical activity on child health, growth and development.
- A Center of Research Translation in Muscular Dystrophy Therapeutic Development. Funded by NIAMS in September 2016, this new Center complements other longstanding NIAMS contributions to muscular dystrophy research, such as leadership of the Muscular Dystrophy Coordinating Committee, and support for the Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Centers program.
- The Brittle Bone Disorders Rare Disease Clinical Research Consortium. In partnership with other NIH Institutes and Centers, NIAMS supports this multi-center effort to advance research that will improve treatment and care for osteogenesis imperfecta, a group of genetic bone disorders that manifest in early life.
The NIAMS Intramural Research Program (IRP) has a long-standing commitment to conducting pediatric rheumatology research, and, as mentioned in my letter last month, supporting training in pediatric rheumatology through a program with Children’s National Medical Center in Washington, D.C. The IRP Pediatric Translational Research Branch seeks to understand the cellular and molecular mechanisms of juvenile spondyloarthritis, an inflammatory disease that affects the joints as well as the entheses—sites where ligaments and tendons attach to bone. The IRP Translational Genetics and Genomics Unit (TGGU) is exploring the mechanisms involved in inflammatory and autoimmune diseases, such as systemic juvenile arthritis and Behçet's disease. As part of the International Childhood Arthritis Genetics (INCHARGE) consortium, intramural researchers within the TGGU along with others at NIH contributed to a genome-wide association study that recently reported on genetic regions associated with increased risk of systemic juvenile idiopathic arthritis.
In addition to funding pediatric research through centers, large initiatives, and the IRP, NIAMS also supports research on rare diseases in children through research project grants. In November 2016, NIAMS-funded extramural researchers published preliminary results from a phase 1 clinical trial of gene therapy for recessive dystrophic epidermolysis bullosa, a rare blistering skin disease with symptoms beginning in infancy. Earlier in 2016, NIAMS grantees reported new findings that advance understanding of fibrodysplasia ossificans progressiva, a debilitating genetic disorder that causes excess bone formation.
These are only a few examples of the progress we are making towards improving the lives of children. We will continue pursuing new knowledge to help every child have a healthy start in life and improve the Nation’s long-term health.
Stephen I. Katz, M.D., Ph.D.
National Institute of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health