NOT-AG-22-032: Notice of Special Interest: Development of Radiotracers for Diagnosis and Clinical Studies in Alzheimer's Disease (AD) and AD-Related Dementias (ADRD)

Notice of Special Interest: Development of Radiotracers for Diagnosis and Clinical Studies in Alzheimer's Disease (AD) and AD-Related Dementias (ADRD)

Notice Number:

NOT-AG-22-032

Key Dates

Release Date:

September 28, 2022

First Available Due Date:

January 05, 2023

Expiration Date:

September 05, 2025

Related Announcements

PAR-20-037 - Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Not Allowed)

PAR-20-038 - Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional)

PAR-20-309 - Alzheimer's Clinical Trials Consortium (ACTC) Clinical Trials (R01 Clinical Trial Required)

PAR-22-047 - Alzheimer's Drug-Development Program (U01 Clinical Trial Optional)

PAR-22-093 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)

PAR-22-094 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R21 Clinical Trial Optional)
PAS-22-196 - Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional)

PAS-22-197 - Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional)

Issued by

National Institute on Aging (NIA)

Purpose

This Notice of Special Interest (NOSI) invites applications for research grants that propose to develop radiotracers for Positron Emission Tomography (PET) for use in Alzheimer's disease (AD) and AD-related dementias (ADRD) research targeting new and/or emerging biological process or molecular pathways that have been shown to be relevant in the etiology and pathophysiology of neurodegeneration.

Background

Radiotracers are instrumental in clinical studies as tools for drug development, as well as to study disease pathophysiology in living human subjects. PET tracers that are widely used for clinical research in AD/ADRD allow imaging two major pathological landmarks of disease, that is, Amyloid beta and tau-proteinopathies. Additionally, PET tracers are critical for differential diagnosis and prognosis in different dementia syndromes, as well as in clinical trials, for patient selection and as response biomarkers. However, evidence from mechanistic studies, genomics and other omics strongly suggest the involvement of multiple cellular processes and biochemical pathways in the etiology and pathophysiology of AD/ADRD, as well as the contribution of different organelles and cell types. Hence, there are tremendous opportunities for development of PET imaging tracers that bind to unexplored, emerging targets. Moreover, different molecular species and supramolecular structures are found —alone or in combination— in pathological aggregates in different forms of dementia, which could be selectively targeted with novel tracers.

Objectives

This NOSI invites applications that propose to develop PET Radiotracers suitable for use in AD and ADRD research in human subjects as biomarkers or in drug development. The research should focus on new and/or emerging targets associated with biological processes and/or molecular pathways relevant in the etiology and pathophysiology of neurodegeneration. Approaches may include both novel tracers, as well as the repurposing/pharmacodynamic and/or emission improvement of existing tracers for use in AD/ADRD research in humans. Leveraging multi-omic datasets, such as Agora's targets database or other publicly accessible resources, for the prioritization of candidate targets for ligand development is encouraged, but not required. Both clinical and preclinical studies may be supported by this NOSI. For clinical (human) studies, exploration of tracers’ properties and performance in heterogeneous populations is strongly encouraged. For preclinical studies, consideration for biological variation due to heterogeneity in the human population, such as the use of biological samples and autoptic tissues from donors of different backgrounds, is also suggested. Candidate targets include, but are not limited to, molecules pertaining to the following biological domains:

Immune response
Endolysosomal trafficking
Mitochondrial metabolism and homeostasis
Synaptic Function
Cell structure stabilization
Epigenetic regulation
Oxidative stress
Regulation of Apoptosis
Vascular function
Myelination
Lipid metabolism
RNA Spliceosome
Proteostasis
DNA damage and repair
Cell cycle
Autophagy

Available Resources

To learn more about target datasets, cellular and animal models, and human data and specimen repositories, applicants are encouraged to explore the following list of available resources:

Application and Submission Information

This notice applies to due dates on or after January 5, 2023 and subsequent receipt dates through September 5, 2025.

Submit applications for this initiative using one of the following funding opportunity announcements (FOAs) or any reissues of these announcements through the expiration date of this notice.

PAR-20-037 - Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Not Allowed)
PAR-20-038 - Development and Application of PET and SPECT Imaging Ligands as Biomarkers for Drug Discovery and for Pathophysiological Studies of CNS Disorders (R01 Clinical Trial Optional)
PAR-20-309 - Alzheimer's Clinical Trials Consortium (ACTC) Clinical Trials (R01 Clinical Trial Required)
PAR-22-047 - Alzheimer's Drug-Development Program (U01 Clinical Trial Optional)
PAR-22-093 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R01 Clinical Trial Optional)
PAR-22-094 - Research on Current Topics in Alzheimer's Disease and Its Related Dementias (R21 Clinical Trial Optional)
PAS-22-196 - Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R43/R44 Clinical Trial Optional)
PAS-22-197 - Advancing Research on Alzheimer's Disease (AD) and Alzheimer's-Disease-Related Dementias (ADRD) (R41/R42 Clinical Trial Optional)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

For funding consideration, applicants must include “NOT-AG-22-032” (without quotation marks) 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 not be considered for the NOSI initiative.

Inquiries

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

Scientific/Research Contact(s)

Lorenzo M. Refolo, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-594-7576
Email: refolol@nia.nih.gov

Alessandra C. Rovescalli, Ph.D.
National Institute on Aging (NIA)
Phone: (301) 402-7503
Email: rovescaa@mail.nih.gov