Notice Number: NOT-AG-14-009

Key Dates
Release Date: February 21, 2014
Estimated Publication Date of Announcement: April 4, 2014
First Estimated Application Due Date: June 4, 2014
Earliest Estimated Award Date: September 15, 2014
Earliest Estimated Start Date: September 15, 2014

Related Announcements
None

Issued by
National Institute on Aging (NIA)

Purpose

Key recommendations from the NIH Alzheimer’s Disease (AD) Research Summit 2012: Path to Treatment and Prevention related to overcoming the underlying causes of failure of AD drugs in the clinic and attaining the goal of precision medicine for AD (treating the right patient with the right drug at the right stage of the disease) called for development of broad capabilities and infrastructure in quantitative systems pharmacology (QSP) to understand the impact of drugs on organisms in a precise and predictive manner in order to determine dosing, reduce toxicity, and enable rational drug repurposing and development of combination therapies. QSP is an emerging model-based, data-driven approach to drug development that integrates systems biology with pharmacology and breaks decisively with a “one-gene, one-receptor, one-mechanism” approach in favor of a network-centric view of drug targets and drug action. A general framework for the development and implementation of a QSP approach has been provided by the NIH QSP Workshop Group (http://www.nigms.nih.gov/News/Reports/201110-syspharma.htm).

In response to the above recommendations and in order to achieve key research milestones of the National Plan to Address Alzheimer’s Disease (http://aspe.hhs.gov/daltcp/napa/milestones/milestones-i.pdf ), the National Institute on Aging at the NIH plans to establish up to two translational centers which will apply QSP approaches to AD drug discovery and development. By integrating multidimensional /multiscale data analysis with mathematical modeling and empirical testing throughout preclinical and early clinical development, this translational center initiative will aid the validation of novel targets through clinical proof of mechanism, the design and selection of candidate therapeutics, the development of predictive biomarkers of efficacy and toxicity, and the selection of patients most likely to respond to single therapeutic agents or combinations of agents. The translational centers initiative is planned for fiscal year 2016; it will use the U54 cooperative agreement mechanism for a multi-component specialized center.

The Center(s) will have/develop the following capabilities:

• conduct quantitative analysis of the effects of small molecules and biologic drugs on therapeutic targets across multiple scales of complexity
• investigate the origins of variability in drug response at the single-cell, organ and patient level that arise from differences at the level of the proteome, genome and environment
• generate and/or exploit diverse “omic” data collected in humans and various animal models to identify translatable pharmacodynamic biomarkers and enable modeling of drug response determinants in distinct patient populations
• develop multi-scale computational models of pharmacological mechanism that bridge the divide between cell-level biochemical models and organism-level PK/PD models
• develop systems approaches for comprehensive and systematic failure analysis during preclinical and clinical drug development
• enable rapid and broad sharing of data, analytical and research tools and models prior to publication

The translational center(s) will bring together expertise in various high-throughput ‘omic’ technologies, acquisition, integration and analysis of multiscale data, mathematical modeling, structural biology, medicinal chemistry, chemo-informatics, PK/PD modeling, pharmacology, trial design and failure analysis.

Realizing the challenges in bringing together the groups with required expertise to develop a competitive center application, NIA intends to support P20 planning grants which will facilitate the development of necessary multi-institutional and/or multi-sector (academia, industry, and non-profit organizations) collaborations and partnerships.

This Notice encourages investigators from institutions and organizations with relevant expertise and capabilities to begin to consider developing relevant collaborations/partnerships to apply for a planning grant.

The intended planning grant FOA will utilize the P20 activity code. Details of the FOA are provided below.

Research Initiative Details

The Planning Grant (P20) FOA will support planning for the development of a full application for a multi-institutional and/or a multi-sector translational center that will fulfill the above-described programmatic goals. These onetime, 1 year awards will support a variety of planning activities necessary to develop relevant collaborations and capabilities, but it will not support direct research activities. The direct costs budget for the planning grant (P20) is limited to $200,000. NIA anticipates awarding up to 4 planning grants depending on the quality of the planning grant applications and availability of funds.

APPLICATIONS ARE NOT BEING SOLICITED AT THIS TIME.

Inquiries

Please direct all inquiries to:

Suzana Petanceska, Ph.D.
National Institute on Aging (NIA)
Telephone: 301-496-9350
Email: petanceskas@nia.nih.gov