National Institute on Aging (NIA)
The National Institute on Aging (NIA) intends to issue a Notice of Funding Opportunity (NOFO) inviting U54 Cooperative Agreement applications aiming to establish multi-component Alzheimers Disease and Related Dementias Translational Centers for Microphysiological Systems (MPS) (AD/ADRD MPS Translational Centers). The overarching purpose of this Centers program is to develop 2D and 3D models of AD/ADRD as reproducible and scalable platforms that recapitulate key features of human AD/ADRD pathophysiology to be used as precision medicine research tools to investigate the complex biology of AD/ADRD and to accelerate multiple aspects of drug discovery and preclinical drug development.
To this end, the funded Centers will focus on the development and validation of 2D and 3D MPS models of AD/ADRD, conduct extensive characterization and deep phenotyping of these 2D and 3D MPS models, discover and characterize translatable biomarkers, and develop standardized methods to facilitate the assessment of bioavailability, efficacy, and toxicity of candidate therapeutic agents. Central to this initiative are the rapid dissemination of 2D and 3D MPS models and transparent reporting of research methodology and preclinical safety and efficacy testing findings to all qualified researchers for their use in basic research and preclinical therapy development. To achieve these goals, the Centers will need to bring together experts in AD/ADRD disease biology, bioengineering, microfluidics, material science, systems biology, computational biology, electrophysiology, pharmacology, biostatistics, and clinical science.
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The NOFO is expected to be published in Fall 2023 with an expected application due date in Winter 2024.
This NOFO will utilize the U54 Specialized Center- Cooperative Agreements activity code. Details of the planned NOFO are provided below.
The overarching objective of this initiative is to create AD/ADRD MPS Translational Centers focused on establishing an infrastructure to develop standardized and deeply phenotyped 2D and 3D MPS models, establishing the translational validity of these MPS models to recapitulate the molecular and network perturbations identified in AD/ADRD, and ensuring rapid and broad distribution of the MPS models, data, and analytical methods for use in basic research and therapy development.
The AD/ADRD 2D and 3D MPS models are expected to express critical aspects of human physiology and provide a measurable output for the representative systems. In developing AD/ADRD disease models that more accurately represent human physiology and pathology, investigators are strongly encouraged to take advantage of recent advances with iPSCs. Essential characteristics of the disease models should include all or some of the following features:
Ideally, the platform used should be compatible with high content screening platforms that include multiple molecular read-outs, such as gene expression, proteomic, metabolomic, or epigenomic analyses. The bioengineered platform should also provide spatial and temporal control of the cellular microenvironment, while enabling continuous monitoring (sensing), probing (direct in-cell measurements), and sampling (testing and continuous data collection and analysis) of the system. Proposals to develop MPS technologies that allow for the testing of potential AD/ADRD therapies in a manner that incorporates development of collections from participants from diverse ancestry and genetic backgrounds are encouraged. It is anticipated that development of MPS representative of human tissues and organs will lead to a reduction in the timelines and costs associated with therapeutic development, and will lead to enhanced efficacy and toxicity information for regulatory decisions.
Overall Organization of the Center
The Center should have the following structure:
Administrative and Data Management Core: will serve as the focus for the synergistic activities of the Center and will be responsible for managing, coordinating, and supervising the entire range of Center activities. This includes monitoring progress, ensuring that the overall project management plan is effectively implemented, and ensuring that yearly milestones are achieved within proposed timelines. In addition, the Core will be responsible for maintaining both an internal and an outward-facing, publicly available website housing data generated by the Center, as well as for oversight for open-access sharing and distribution of MPS models, methods, and data to all qualified scientists from the academic and biopharma communities.
Bioinformatics and Computational Biology Core: will develop and deploy analytical tools and methods that enable the characterization and standardization of MPS models for experimental validation relative to human AD/ADRD outcomes. For this purpose, the Core will use both standard and innovative biostatistics, bioinformatics, and computational biology approaches to analyze and interpret high-dimensional data generated in the MPS models and their integration/alignment with relevant human data. The Core, in conjunction with the Administrative and Data Management Core, will share responsibility for creating and maintaining both an internal and an outward-facing, publicly available website housing data generated by the Center and ensure the rapid and broad sharing of data and analytical results.
MPS Models Development and Validation Core: will be responsible for the development, characterization, and deep phenotyping of new 2D and 3D MPS models in comparison with various molecular, biochemical, and cellular pathological features of human AD/ADRD, including representation of population heterogeneity.
Preclinical Efficacy and Safety Core: will be responsible for developing and implementing rigorous best practices for preclinical safety and efficacy testing of candidate therapeutics and testing promising preclinical candidates in AD/ADRD MPS models. Emphasis should be placed on using translatable biomarkers that inform the level of target engagement as endpoints to determine the widest possible therapeutic window that will support testing a full dose range in humans.
NIA intends to commit up to $7 million in fiscal year 2025.
NIA intends to fund 2 awards.
An application may request a budget of up to $2.5 million direct costs per year. Budgets should reflect the actual needs of the proposed project.
Applications are not being solicited at this time.
Please direct all inquiries to:
Zane Martin, Ph.D.
National Institute on Aging (NIA)