Background

The INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018 and 2019 Omnibus Appropriations Reports, which encouraged the NIH to expand its current efforts on Down syndrome (DS) and common co-occurring conditions also seen in the general population while increasing the pipeline of DS investigators. Information about projects that were funded in 2018 and 2019, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with DS face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though 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. In addition to intellectual disability, DS is associated with an increased prevalence of autism and epilepsy. About 75% of individuals with DS experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with DS also have high rates of hearing loss, eye abnormalities, congenital heart defects, sleep apnea, pulmonary hypertension, gastrointestinal malformations, thyroid disease, leukemia, and other autoimmune or immune dysregulation disorders including celiac disease. However, people with DS infrequently develop solid tumors such as breast or prostate cancer. Despite multiple risk factors for coronary artery disease and high rates of obesity, sleep apnea, and type 1 diabetes, people with DS rarely develop atherosclerosis or have myocardial infarctions. Understanding this unique combination of risk and resiliencies will inform medical advances for individuals with DS and for individuals who do not have DS but who share these co-occurring conditions.

Research Objectives

This Notice of Special Interest (NOSI) announces NIH support for the professional development of early career scientists aiming to establish a career in DS-related research. By providing these scientists with training, resources, and mentorship, the NIH intends to foster a pipeline of investigators in DS and other intellectual disabilities who will lead future research to improve the understanding of the biology of DS and support development of new treatments for health conditions experienced by those with DS.

The NIH is issuing this NOSI to expand the community of investigators conducting research related to DS by encouraging scientists and physicians early in their research careers to develop research projects related to co-occurring conditions associated with DS. Sharing of resources and effective communication of outputs to the broader communities are a high priority of the INCLUDE Project. Applicants responding to this NOSI are strongly encouraged to describe plans for rapid sharing of data and results as well as innovative data analytics approaches (see Goal 3, NIH Strategic Plan For Data Science).

A list of Funding Priorities by Institute and Center for the project is available on the INCLUDE website. Applications in response to this NOSI should be aligned with the overall INCLUDE Project Research Plan, which consists of three components:

• Component 1: Targeted, high risk-high reward, basic science studies in areas highly relevant to Down syndrome
• Component 2: Cohort Study to connect existing resources and expand to inclusion of individuals with Down syndrome
• Component 3: Inclusive clinical trials research for co-occurring conditions in individuals with Down syndrome

Projects that propose to recruit subjects with DS are encouraged to promote enrollment of research subjects in the DS patient registry supported by NIH, DS-Connect . For other data and biospecimens from human genetic or non-genetic studies, awardees are encouraged to use biorepositories designated by INCLUDE staff that meet requirements for broad sharing. An NIH resource describing Common Data Elements may be helpful during the planning phases of a project when considering ways to optimize data collection in order to facilitate broad data sharing.?

Application and Submission Information

This Notice applies to due dates on or after February 12, 2020 and expires on January 8, 2022.

Applications in response to this NOSI must be submitted using one of the following target Funding Opportunity Announcements (FOAs) or their reissued equivalents. Although not all NIH components indicated above are listed as Participating Organizations in all FOAs listed below, applications for this special topic will be accepted.

Activity Code	FOA	First Available Due Date
K01	PA-19-126 Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Not Allowed)	Feb 12, 2020
K01	PA-19-127 Mentored Research Scientist Development Award (Parent K01 - Independent Clinical Trial Required)	Feb 12, 2020
K01	PA-19-084 Mentored Research Scientist Development Award (Parent K01 Independent Basic Experimental Studies with Humans Required)	Feb 12, 2020
K08	PA-19-116 Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Clinical Trial Required)	Feb 12, 2020
K08	PA-19-117 Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Clinical Trial Not Allowed)	Feb 12, 2020
K08	PA-19-086 Mentored Clinical Scientist Research Career Development Award (Parent K08 Independent Basic Experimental Studies with Humans Required)	Feb 12, 2020
K23	PA-19-118 Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Clinical Trial Required)	Feb 12, 2020
K23	PA-19-119 Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Clinical Trial Not Allowed)	Feb 12, 2020
K23	PA-19-087 Mentored Patient-Oriented Research Career Development Award (Parent K23 Independent Basic Experimental Studies with Humans Required)	Feb 12, 2020
K99/R00	PA-19-129 NIH Pathway to Independence Award (Parent K99/R00 Independent Clinical Trial Required)	Feb 12, 2020
K99/R00	PA-19-130 NIH Pathway to Independence Award (Parent K99/R00 - Independent Clinical Trial Not Allowed)	Feb 12, 2020
K99/R00	PA-19-090 NIH Pathway to Independence Award (Parent K99/R00 Independent Basic Experimental Studies with Humans Required	Feb 12, 2020

All instructions in the SF424 (R&R) Application Guide and the listed funding opportunity announcements must be followed, with the following additions:

• For funding consideration, applicants must include NOT-OD-20-021 in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will be withdrawn from consideration for this initiative.

Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

A list of contacts for each participating NIH Institute and Center is available on the INCLUDE website.