SOW_75N95021Q00286.pdf

Version 11-30-2016-1 FAR Part 11—Describing Agency Needs

STATEMENT OF WORK (SERVICES)

(SOW)

GENERAL INFORMATION

Title of Project:

Testing the efficacy of candidate Alzheimer’s disease treatments in rescuing impaired hippocampal synaptic plasticity 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 an ongoing 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 will test approximately 20 drugs that NIA have nominated as ‘candidate AD treatments.’ NIA will select the most promising drugs from the DREAM study that lower AD risk for in vivo efficacy studies in a transgenic mouse model of AD. In the proposed acquisition, NIA will test the efficacy of the most promising drugs emerging from the DREAM study and ongoing proteomic/metabolomic studies in the NIA IRP to rescue 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 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. As part of the DREAM study, NIA will perform pharmacoepidemiologic analyses of approximately 20 FDA approved drugs to test whether older individuals exposed to these ‘candidate AD treatments’ are at lower risk of AD. In parallel with these analyses, NIA also test whether these drugs ameliorate pathological changes associated with AD at the cellular level. In the next stage of these analyses, NIA proposes to select the most promising drug(s) for testing as disease-modifying AD treatments by assessment of their efficacy in rescuing impaired hippocampal synaptic plasticity using the APP/PS1 transgenic mouse model of AD.

Period of Performance:

September 30, 2021 – September 29, 2023 This contract represents a project which is a single undertaking with a defined end-product that cannot feasibly be subdivided for separate performance. The main objectives of the project are to identify promising candidate drugs of Alzheimer's disease through electrophysiological recordings of hippocampal synaptic plasticity. These data from five (5) candidate AD drugs must be fully acquired over the indicated time period before they are analyzed together. The data cannot be subdivided as the scientific rationale for the study is based on a combined analysis of all the data together.

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 candidate AD drugs rescue 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(s) 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(s).

Specific Requirements:

LEVEL OF EFFORT:

Research associate 2000 labor hours for period of performance.

GOVERNMENT RESPONSIBILITIES

Provide a list of five (5) ‘candidate AD treatments’ i.e. ‘drugs’ 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 says 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 9/30/2021 through 9/29/2023. 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.