Funding Opportunities

The purpose of this funding opportunity announcement (FOA) is to support hypothesis-driven research to discover human biomarkers in Parkinson’s disease and other Parkinsonian syndromes, as a component of the NINDS Parkinson’s Disease Biomarkers Program (PDBP). This FOA encourages biomarkers discovery projects in: 1) genetically causal Parkinson's disease, especially for particular sub-types of Parkinson's Disease (PD), including genetic cohorts, biologically defined cohorts of idiopathic PD, or ethnic subgroups of idiopathic PD; 2) the differentiation of synucleinopathies (such as PD and Multiple System Atrophy (MSA) from tauopathies (such as  Progressive Supranuclear Palsy and Corticobasal degeneration); or 3) to improve diagnostic differentiation between idiopathic/subtypes of PD and these disorders, as well as from Essential tremor. To further advance research in this area, broad sharing of biospecimens and associated data is a critical feature of the PDBP generally and of this FOA specifically. A timeline including milestones, which will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years, is required for all studies.

The purpose of the Lewy Body Dementia Center Without Walls (CWOW) program is ultimately to understand how toxic species of alpha-synuclein and amyloid-beta produce the clinical pathology characteristic of Lewy Body Dementia.  This FOA invites applications that will systematically and comprehensively characterize alpha-synuclein and amyloid-beta subspecies found in human LBD post-mortem brain tissue, identify toxic subspecies and potential mechanisms of toxicity, and characterize any interactions between the proteins that may contribute to increased toxicity and/or explain selective vulnerabilities of cells/circuits.  Given the heterogeneity of both alpha-synuclein and beta-amyloid subspecies, applicants will be expected to focus on the use of post-mortem brain tissue from subjects with LBD; human neuronal cultures/slices/organoids, and human blood/stem cells/CSF from subjects with LBD may also be used for this purpose.  It is expected that a multi-site, multidisciplinary team with expertise in 1) mapping neuronal protein structure, function, and interactions at multiple levels, and 2) elucidating neurodegenerative mechanisms that are likely to be relevant to LBD, will be necessary.  All centers will be expected to produce a publicly-available library of fully characterized alpha-synuclein and amyloid-beta subspecies found in LBD.

The goal of this funding opportunity announcement (FOA) is to support collaborative translational research projects aligned with NIH efforts to enhance the translation of basic biological discoveries into clinical applications that improve health. This opportunity is specifically to promote partnerships between NIH intramural investigators (e.g., those conducting research within the labs and clinics of the NIH) and extramural investigators (e.g., those conducting research in labs and clinics outside of the NIH).  It will provide support for extramural investigators to take advantage of the unique research opportunities available at the NIH Clinical Center (http://www.cc.nih.gov/translational-research- resources/resources.html) by conducting research projects in collaboration with NIH intramural investigators.

While translating basic research into clinical practice is increasingly difficult, time consuming, and expensive, translational research is crucially important in converting basic scientific discoveries into new diagnostics and therapies for patients.  As such, this FOA intends to broaden and strengthen translational research collaborations between basic and clinical researchers both within and outside NIH to accelerate and enhance translational science. All teams must have at least one intramural and one extramural investigator.

This program will provide access for external researchers to the NIH Clinical Center and will leverage the diverse Clinical Center resources, expertise, and infrastructure available to test promising laboratory- and animal-based discoveries with potential implications for disease diagnosis, treatment and prevention. The NIH Clinical Center is a hospital exclusively dedicated to clinical research, thus research is the culture and research studies are routine. Its mission includes the support of clinical studies that are considered intellectually challenging and risky but with the potential of high reward with new breakthroughs in medicine. The special environment of the Clinical Center supports studies that may not be readily supported elsewhere. This may include collaborations that propose targeted increases in new patients enrolled in protocols at the Clinical Center. 

Examples of the special resources of the Clinical Center include:

• Large cohorts of patients, including studies of >500 rare diseases;
• The manufacturing and use of newly designed PET ligands for imaging studies; The availability of blood products for special research studies;
• Collaborative opportunities on clinical protocols (http://clinicalstudies.info.nih.gov/) on unique pharmaceutical agents and/or other modes of therapy, or extraordinarily rare diseases with investigators who are known experts;
• A robust training curriculum in clinical research;
• The ability to support long-term clinical studies at minimal cost to patients and their families.
• On-campus amenities (e.g., Family Lodge and Children's Inn to assist patients and families in supportive, home-like environments as they leave their own homes to participate in clinical research; and
• A number of other resources

For entry to the program, projects must have a collaborating Investigator in the NIH Intramural Program.  As a collaborative partner, the intramural investigator will be actively involved in the planning and execution of the research project.

Applications for this program will be submitted by the extramural institution with the participation of the intramural investigator(s) integrated into the application as described in the Collaboration Plan, and with the budget requirements for the NIH Clinical Center and intramural investigators included in the Budget form of the application.  Funded projects will include an award to the applicant organization which will exclude funds to support the participation of the Clinical Center.  Support for intramural participation will first be determined, then provided if applicable by a budget allocation within the NIH.  Annual progress reports will be prepared and submitted by the extramural institutions, with the participation and input of the intramural investigator(s) and should include the project findings, publications, impact of the project, a description of which Clinical Center unique resources were utilized and any new intramural- extramural partnerships that developed.

The purpose of the FOA is to support the identification of targets and pathways impacting the pathophysiology of ADRDs, through use of large scale robust and reproducible molecular platforms and extensively phenotyped human brain tissue, biosamples and cell resources.

The purpose of this FOA is to support the structural characterization and validation of protein species (Tau, alpha-synuclein, TDP43, progranulin/granulin, FUS, and beta-amyloid) related to ADRD pathophysiology.  Recent advances in cryo-EM and cryo-ET enable analysis of protein species present in frozen autopsy tissues and the dynamics of protein aggregation and subcellular localization in human cell sources, respectively. As these technologies continue to evolve, collaboration across laboratories will be necessary to develop robust protocols for validation of cryo-EM structures.  This FOA supports the resolution of ADRD-associated protein species, collaboration with other investigators through an ADRD proteinopathy consortium, and the validation of new structural entities through development of tools to detect the abundance and dynamics of these protein species in human tissue, appropriate animal models and in human cell-based neurological model systems.

The purpose of this Notice is inform applicants of the new expiration date of PAR-16-112, "Biomarkers Discovery in Parkinsonism (U01)" on January 24th, 2018.  NINDS plans to reissue this Funding Opportunity Announcement (FOA) for compliance with FORMS-E.