Evaluation of Exenatide in a MitoPark Mouse Model of Parkinson¡¯s Disease

Agency: HEALTH AND HUMAN SERVICES, DEPARTMENT OF
State: Ohio
Type of Government: Federal
FSC Category:
  • 29 - Engine Accessories
NAICS Category:
  • 541990 - All Other Professional, Scientific, and Technical Services
Posted Date: Aug 7, 2020
Due Date: Aug 19, 2020
Solicitation No: HHS-NIH-NIDA-75N95020Q00171
Bid Source: Please Login to View Page
Contact information: Please Login to View Page
Bid Documents: Please Login to View Page
Evaluation of Exenatide in a MitoPark Mouse Model of Parkinson’s Disease
Active
Contract Opportunity
Notice ID
HHS-NIH-NIDA-75N95020Q00171
Related Notice
Department/Ind. Agency
HEALTH AND HUMAN SERVICES, DEPARTMENT OF
Sub-tier
NATIONAL INSTITUTES OF HEALTH
Office
NATIONAL INSTITUTES OF HEALTH NIDA
General Information View Changes
  • Contract Opportunity Type: Presolicitation (Updated)
  • All Dates/Times are: (UTC-04:00) EASTERN STANDARD TIME, NEW YORK, USA
  • Updated Published Date: Aug 06, 2020 09:48 am EDT
  • Original Published Date: Aug 04, 2020 02:48 pm EDT
  • Updated Response Date: Aug 19, 2020 02:00 pm EDT
  • Original Response Date: Aug 19, 2020 02:00 pm EDT
  • Inactive Policy: 15 days after response date
  • Updated Inactive Date: Sep 03, 2020
  • Original Inactive Date: Sep 03, 2020
  • Initiative:
    • None
Classification
  • Original Set Aside:
  • Product Service Code: B529 - SPECIAL STUDIES/ANALYSIS- SCIENTIFIC DATA
  • NAICS Code: 541990 - All Other Professional, Scientific, and Technical Services
  • Place of Performance:
    Cleveland , OH 44106
    USA
Description

INTRODUCTION:

PURSUANT TO FAR Subpart 5.2-Synopses of Proposed Contract Actions, THIS IS A PRE-SOLICITATION NOTICE OF A PROPOSED CONTRACT ACTION.

THIS IS A PRE-SOLICITATION NON-COMPETITIVE NOTICE OF INTENT TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME).

The National Institute on Drug Abuse (NIDA), Office of Acquisition, Contracts Management Branch Blue, NIA Section on behalf of the National Institute on Aging intends to negotiate and award a purchase order to the Case Western to perform the evaluation of Exenatide in a MitoPark mouse model of Parkinson’s disease.

North American Industry Classification Systems (NAICS) Code
The intended procurement is classified under NAICS code 541990 with a Size Standard of $16.5 million.

Regulatory Authority
The resultant contract will include all applicable provisions and clauses of the Federal acquisition Regulation (FAR) in effect through the Federal Acquisition Circular (FAC) 2020-06, dated May 6, 2020.

Statutory Authority
This acquisition is conducted as non-competitive under the authority of 41 U.S.C. 253(c) under provisions of the statutory authority of FAR Subpart 6.302-1 -- Only One Responsible Source and No Other Supplies or Services Will Satisfy Agency Requirements.

This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures, Subpart 13.106-1 (b) (1), Soliciting from a single source.

Background and Objectives:

Parkinson’s disease (PD) affects 6 million people worldwide. Currently available symptomatic treatments for PD primarily focus on stimulation of dopaminergic signaling and can provide symptomatic relief for a limited time but have little effect on nonmotor symptoms, and none have been shown to affect the progressive pathological and clinical decline. Thus, alongside the need to develop more effective symptomatic therapies for PD, the greatest unmet need for patients, caregivers, and healthcare systems is the development of a disease-modifying treatment for PD.

The goal is to provide multiple lines of evidence to suggest that the type 2 diabetes mellitus drug, Exenatide, may be useful in the treatment of PD [1,2,3]. Preclinical evidence predicting the efficacy of Exenatide and alike drugs in the treatment of human PD has derived from relatively short-term animal studies involving the administration of dopaminergic toxins such as 6-hydroxydopamine, LPS and MPTP that, relatively rapidly, induce dopaminergic neuron dysfunction and death [1,2,3]. Although valuable, such models do not mimic the long-term progressive loss of dopaminergic neurons found in human PD and aligns with the slow onset of Parkinsonism in afflicted individuals.

Project Requirements:

Evaluate the efficacy of an approved and well tolerated type 2 diabetes Mellitus drug, Exenatide, in a disease progressive mouse model of Parkinson’s disease – the MitoPark mouse that has parallels to the human disorder.

An interesting and well characterized preclinical model that mimics many aspects of the human disorder is the MitoPark mouse in which a selective and progressive degeneration of dopamine neurons occurs within the substantia nigra leads to adult onset degeneration of nigrostriatal dopamine circuitry with resulting motor deficits that can be mitigated by L-DOPA administration. This degeneration is induced by a cell type-specific inactivation of mitochondrial transcription factor A, a protein indispensable for mitochondrial DNA expression and preservation, within dopamine neurons that leaves them respiratory chain deficient. The focus of this contract is to evaluate the efficacy of Exenatide in the MitoPark mouse model of PD.

Specifics:

The preclinical evaluation of Exenatide in a MitoPark mouse model of Parkinson’s disease.

The SOW includes outcome measures:

  1. Histochemical
  2. Behavioral
  3. Biochemical

Animals. The breeding scheme for generating MitoPark mice has been described previously (Ekstrand et al. 2007, Galter et al. 2010, [Ref 1, 2, above] and must comply with this. Briefly, MitoPark mice will be generated on a C57BL6 background, in which the DA transporter (DAT) promoter will be used to drive cre-recombinase expression, and these will be crossed with mice in which the Tfam gene has been loxP-flanked. Use of IRES technology allows both DAT alleles to be maintained. All animals used in the studies will be either males or female – but not mixed (due to gender differences in disease progression). Age-matched wild type mice will be used as controls.

Genotyping of mice is essential, and all studies must be undertaken on approved Animal protocols.

Exenatide studies. Exenatide will be provided by the Contractor – specifically by Dr. Nigel H. Greig (TGB/NIA/NIH: Email: Greign@grc.nia.nih) – who will oversee the scientific basis of the project. The Exenatide will be in the form of the sustained release form, PT320. This will be clinical grade material and will be administered subcutaneously once every two weeks.

  1. The dose of PT320 will be 0.6 mg/kg, subcutaneously once every 2 weeks.
  2. As Exenatide represents only 2% of the drug available within the formulation of PT320 (the remaining 98% is polymers from which it is slowly released from), the total amount of material used is 30 mg/kg of PT320. (This is equivalent to 0.6 mg/kg of Exenatide).

Notably, the PT320 microsphere powder will NOT go into solution – but will form a suspension. It is important to ‘vortex’ just before injecting the PT320 into animals, and that the PT302 material is in suspension immediately prior to each injection

Behavioral Studies

Locomotor activity. 5-10-week-old mice will be habituated to a low-noise experimental environment for 1 h and then placed in an open-field chamber (20 cm x 30 cm x 30 cm) in this environment. A digital camera will be mounted on the ceiling to allow filming the animals while moving freely for 1 hour. The videos will be analyzed by dedicated software (TopScan®, Clever Sys Inc., VA, USA) to detect rodent movements and behaviors based on video-tracking of multiple individual body parts, posture and frequency of movements. The horizontal movements for 1 hour were taken as distance traveled.

Cylinder test. The cylinder test will be performed to evaluate vertical movements and axial set. The mice will be habituated to a low-noise experimental environment for 1 h. After habituation, the mice will be placed in an open-top, clear plastic cylinder (diameter: 20 cm, height 30 cm) for 5 min and behavior recorded by a video camera. Rearing will be counted from video records.

Rotarod test. Rotarod tests will be performed to evaluate motor coordination and balance. During a training phase, mice will be introduced to walking on the rotating rod (47650 Rota-Rod NG, Ugo Basile, Comerio, Italy) one day before being tested. The training will be completed when all mice were able to walk forward for 720 s at 15 rpm. The accelerating speed (from 5 rpm to 80 rpm within 240 s) rotarod test will be performed 3 times a day every 2 weeks. The time until the animal falls off the rotating rod will be recorded by observers blinded to the mice genotypes. Trials will be separated by at least 30 min.

[18F]FE-PE2I PET scan imaging for Dopamine Transporter function (or alternative imaging -depending on approval of Dr. Greig TGB/NIA/NIH). Longitudinal imaging studies will be performed to evaluate the dopaminergic system in brain at approx. 8 and 16 weeks

NAc and striatal brain slice preparation. Brain will be were prepared as described previously (Chen et al. 2008, Good et al. 2013) for evaluation of immunohistochemistry in NAc and striatal brain slices. Tyrosine hydroxylase levels will be evaluated at approx. 8 and 20 weeks

Fast scan cyclic voltammetry and dopamine measurements in brain slices. FSCV recording will be performed as described previously (Chen et al. 2017, Cho et al. 2006) at 8 and 12 weeks.

Statistics. Statistical analyses of data for DA release input/output curves and behavioral tests will be performed using a two-way analysis of variance (ANOVA) followed by a Bonferroni post hoc test for multiple comparisons. All statistical tests will be two-tailed and performed using appropriate software (GraphPad Prism 5.02, GraphPad Scientific, San Diego, CA, USA). A p-value

Level of Effort. Senior scientist with background in neuroscience/neurodegeneration (with M.D., Ph.D. or both) with background in PD and knowledge of GLP-1 receptor agonist drugs

Deliverable:

A research report providing a written overview of the data (Tables and/or graphs/figures), statistical analyses, and short summation of key results – as an electronic file

Anticipated Period of Performance:

The anticipated period of performance is a 12-month base period.

Closing Statement:
This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice.

Responses to this solicitation must include clear and convincing evidence of the offeror's capability of fulfilling the requirement as it relates to the technical evaluation criteria. The price quote must include the labor categories, an estimate of the number of hours required for each labor category, fully loaded fixed hourly rate or each labor category, breakdown and rationale for other direct costs or materials, and the total amount. The technical proposal must include CV information for proposed Key Personnel that meet the minimum requirements specified above.

In addition, the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.
A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

All responses must be received by Wednesday, August 19, 2020 at 2:00 PM Eastern Time and must reference number 75N95020Q00171.

Responses must be submitted electronically to Diedra S. Prophet at diedra.prophet@nih.gov

Fax responses will not be accepted.

"All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency."

Contracting Office Address:

301 N. Stonestreet Ave

Bethesda, Maryland 20892
United States

Place of Performance:

Case Western Reserve University School of Medicine

10900 Euclid Avenue

Cleveland, OH, 44106

Primary Point of Contact:

Diedra S. Prophet

Email: Diedra.prophet@nih.gov

Phone: 301-402-8070

Secondary Point of Contact:

Karon Mahon

Email: Karen.mahon@nih.gov

Phone: 301-435-7479

Attachments/Links
Contact Information
Contracting Office Address
  • c/o 3WFN MSC 6012 301 N Stonestreet Ave
  • Bethesda , MD 20892
  • USA
Primary Point of Contact
Secondary Point of Contact
History

Related Document

Jun 29, 2020[Sources Sought (Original)] Evaluation of Exenatide in a MitoPark Mouse Model of Parkinson’s Disease
Aug 5, 2020[Presolicitation (Original)] Evaluation of Exenatide in a MitoPark Mouse Model of Parkinson’s Disease

Sign-up for a Free Trial, Government Bid Alerts

With Free Trial, you can:

You will have a full access to bids, website, and receive daily bid report via email and web.

Try One Week FREE Now