Program seeks Council approval for an initiative titled “INCLUDE Project Initiatives 2020.” Although Down syndrome (DS) is the most common genetic cause of intellectual and developmental disabilities (IDD), and in the past 25 years, the average lifespan has doubled, from 30 to 60 years, individuals with DS face significant and changing health challenges and have often been excluded from participation in research that could improve their health outcomes and quality of life.
The FY18 Budget appropriation required “a new trans-NIH Down syndrome initiative… to study trisomy 21 [and] to improve the health and neurodevelopment of individuals with Down syndrome and typical individuals at risk for Alzheimer's disease, cancer, cardiovascular disease, immune system dysregulation, and autism, among others.…” In addition, Congress directed NIH in FY19 report language to “continue to make investments in Down syndrome research that prioritize funding for both research grants and early-stage investigators that will expand the current pipeline of Down syndrome research, as well as implementation of the new trans-NIH initiative.” The NIH INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) initiative aims to address these issues by advancing research on Down syndrome in 3 domains: (1) targeted, high-risk, high-reward basic science studies of trisomy 21; (2) assembly of a large clinical cohort of individuals with DS across the lifespan; and (3) inclusive clinical trials research of current and future therapies for co-occurring conditions in DS. It was launched in FY18 with administrative supplements and continued in FY19 with a mixture of R01s, R21s, clinical trials, and supplements.
One proposed FY2020 INCLUDE initiative will focus on projects in the second domain of INCLUDE. These will focus on creating a large clinical cohort of individuals with DS across the lifespan. The goal is to advance the diagnosis, management, and treatment DS and its co-occurring conditions through collection of ‘omics datasets from DS clinical cohorts. This initiative will also facilitate and support the development of a system for the collection, storage and quality control of data related to these conditions in DS as well as an integrated data resource for investigators. Another initiative focusing on research in the second domain of INCLUDE will encourage applicants that propose to conduct secondary analyses of publicly available NIH-funded data sets to enhance our understanding of DS across the lifespan. Some existing DS-related data sets are those collected under the auspices of the Alzheimer’s Biomarkers Consortium–Down Syndrome (ABC-DS) and Gabriella Miller Kids First Pediatric Research Program. Expanded use of existing data sets and biorepositories will allow researchers to address research questions within the scientific scope of the INCLUDE project at relatively low cost and effort and enhance the value of INCLUDE investments in research. An improved understanding of the constellation of co-occurring conditions and resiliencies in individuals with DS will yield a unique opportunity to both address the unmet health needs of individuals with DS while simultaneously improving the health of all individuals.
Another FY2020 initiative will focus on supporting the career development of trainees and early-stage investigators aiming to establish a career in DS-related research. The goal is to support these trainees and early-stage investigators with the training, resources and mentorship to ultimately participate in and enhance DS research that will address all 3 domains of the INCLUDE project. This initiative may include opportunities for institutions and/or individuals to be supported in their training needs. Both investigators early in their careers (e.g., predoctoral candidates) as well as those with advanced degrees (e.g., PhD, MD) may benefit from mentorship from established investigators and professionals in the DS research community in basic science fields as well as clinical and translational arenas. Exceptional training opportunities will ensure the creation of a pipeline of investigators in DS and other intellectual disabilities that will improve understanding of the biology of DS and support development of new treatments for health conditions experienced by those with DS.
These initiatives are being developed by the Office of the Director of NIH, which is supporting and coordinating these activities in FY2020. Due to the large number of participating NIH Institutes and Centers, with up to 18 involved, guidance from the NIH Office of Extramural Research indicated that concept clearance will be required at a single institute. Therefore, NICHD is serving as the institute for clearance for this initiative proposed as part of INCLUDE 2020.
Intellectual and Developmental Disabilities Branch (IDDB)
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