B6 SOW.doc

STATEMENT OF WORK (SOW)

GENERAL INFORMATION

Title of Project:

Testing the efficacy of novel candidate Alzheimer’s disease drugs in rescuing impaired hippocampal synaptic plasticity in the APP/PSI transgenic mouse model Statement of Need and Purpose:

There is currently a pressing need to identify effective treatments for Alzheimer’s disease (AD). With the repeated failures of multiple pivotal phase-III clinical trials in patients with AD, it is critical to test novel methods of discovering disease-modifying AD treatments. As part of a recently completed study called the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study, the National Institute on Aging (NIA) Intramural Research Program (IRP) is testing whether exposure to commonly prescribed, Food and and Drug Administraton (FDA)-approved drugs will be associated with protection against AD. DREAM has tested approximately 20 drugs that NIA have nominated as ‘candidate AD treatments.’ NIA has selected the most promising drugs from the DREAM study to test in the recently funded Experimental Validation of candidate Alzheimer’s disease treatments identified by multi-omics analyses (PREVENT-AD) study. The NIA is additionally testing additional FDA approved and experimental drugs in ongoing contracts including phenotypic screening in cell culture. In the proposed acquisition, NIA will test the efficacy of a promising drug (emerging from the DREAM study, the PREVENT-AD study, ongoing contracts and proteomic/ metabolomic studies in the NIA IRP) to determine whether it rescues impaired hippocampal synaptic plasticity. This will be accomplished by studying their effects on late long term potentiation (LTP) in hippocampal slices obtained from the APP/PS1 transgenic AD mouse model.

Background Information and Objective:

Research in the NIA IRP has identified several FDA approved drugs through the DREAM study that may target metabolic abnormalities associated with AD and be of utility as effective disease-modifying AD treatments. Repurposing of approved drugs is a promising approach that can accelerate the development of novel AD treatments.

Research in the NIA IRP has identified several FDA approved drugs that may target metabolic abnormalities associated with AD and be of utility as effective disease-modifying treatments. Repurposing of approved drugs for AD is a promising approach that can accelerate the development of novel AD treatments. Through two ongoing contracts (75N95021P00404; 75N95023P00649) the NIA is currently testing 9 candidate AD drugs on LTP.

The acquisition objective is to test the efficacy of one candidate AD drug in rescuing impaired hippocampal synaptic plasticity using the APP/PS1 transgenic mouse model of AD.

Period of Performance:

September 30, 2024 – September 29, 2025

SCOPE OF WORK

General Requirements:

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government as needed to perform the Statement of Work below:

The main objective of the requirement is but not limited to the following:

1. Perform in vitro electrophysiological recordings on hippocampal slice preparations from the APP/PS1 AD mouse model and corresponding wild type animal controls in order to test whether a candidate AD drug rescues impairment in late LTP known to occur in this well-characterized AD mouse model.

2. Perform statistical analyses to test whether a candidate AD drug significantly restores impairment in hippocampal synaptic plasticity relative to the vehicle control.

3. Perform additional biochemical/western blot analyses to establish plausible pharmacological mechanisms of drug action associated with rescue of hippocampal plasticity by a drug.

Specific Requirements:

LEVEL OF EFFORT:

Research associate 100 labor hours for period of performance.

GOVERNMENT RESPONSIBILITIES

Specify a ‘candidate AD treatment’ i.e. ‘drug’ to the contractor to enable the performance of the electrophysiological studies detailed above.

DELIVERY OR DELIVERABLES

Detailed report (WORD document) describing methodology, results and interpretation of eletrphysiological studies on hippocampal synaptic plasticity (late-LTP) to be delivered within 364 calendar days of receipt of the list of ‘candidate AD treatments’ by the contractor. The timely submission of this deliverable is essential to successful completing this requirement.

REPORTING REQUIREMENTS

The contractor is required to provide written progress reports every 4 months for the contract period 9/30/2024 through 9/29/2025. The progress report shall cover all work completed during the specified period and shall present the work to be accomplished during the subsequent period. This report shall also identify any problems that arose and a statement explaining how the problem was resolved. This report shall also identify any problems that have arisen but have not been completely resolved and provide an explanation.

Reports shall be as follows;

· WORD document detailing all the technical aspects of the experimental methodology used including dose-response results of the late-LTP experiments and results of any relevant biochemical/western blot analyses.

OTHER CONSIDERATIONS

Key Personnel:

Masters or PhD-level biologist with prior experience in performing electrohysiological experiments from hippocampal slice preparation.

Place of Performance: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore Data Rights:

The National Institute on Aging will have unlimited rights to and ownership of all deliverables provided under this contract including reports, recommendations, briefings, work plans and all other deliverables. This includes the deliverables provided under the basic contract and any optional task deliverables exercised by the contracting officer. In addition, it includes any additional deliverables required by contract change. The definition of “unlimited rights” is contained in Federal Acquisition Regulation (FAR) 27.401, “Definitions.” FAR clause 52.227-14, “Rights in Data-General, ” is hereby incorporated by reference and made a part of this contract/order.

Section 508—Electronic and Information Technology Standards:

The contractor is not required to develop, procure, maintain, or use Electronic and Information Technology (EIT) in the performance of the SOW.

Confidentiality of Information:

The government will not provide to the contractor any information or data of a personal nature about individual(s) or proprietary information or data pertaining to an institution or organization which is confidential.

Version 11-30-2016-1

FAR Part 11—Describing Agency Needs