Contact Points
Cleveland, Ohio 44106
This notice of proposed acquisition is posted as an intent to award a purchase order on a non-competitive basis to the Department of Neurosurgery at Case Western Reserve University School of Medicine for the purpose of services for the Evaluation of Exenatide on mitochondrial function in the MitoPark Parkinson’s disease mouse model.
This acquisition is being conducted under Federal Acquisition Regulations (FAR) Part 13 – Simplified Acquisition Procedures, and FAR Part 12—Acquisition of Commercial Items, and the resultant contract award will include all applicable provisions and clauses in effect through Federal Acquisition Circular 2023-04 dated June 2, 2023.
The purpose of this procurement is to purchase services for the Evaluation of Exenatide on mitochondrial function in the MitoPark Parkinson’s disease mouse model. The National Institute of Health (NIH), National Institute on Aging (NIA), Intramural Research Program (IRP), Translational Gerontology (TG) Branch requires support services to analyze markers of mitochondrial function in a progressive animal model of Parkinson’s disease (MitoPark mouse) to evaluate whether the drug Exenatide provides a potential treatment strategy.
The evaluation of preclinical efficacy of a new treatment strategy to mitigate mitochondrial dysfunction in a progressive mouse model of Parkinson’s disease – to evaluate Exenatide.
Parkinson’s disease (PD) impacts 6 million people worldwide. As it is an age-related neurodegenerative disorder, the figure is estimated to increase to around 10 million by 2030 due to longevity increasing in most Western countries. The social and economic impact on patients and their caregivers is huge and is estimated at $US14.4 billion per year in the USA.
Presently available symptomatic treatments for PD are predominantly directed to enhance dopaminergic signaling and can provide symptomatic relief for a limited time, and none have been shown to impact the progressive pathological and clinical decline. Worldwide, the most widely used and accepted symptomatic treatment for PD is levodopa (L-DOPA). However, levodopa does not mitigate dopaminergic cell dysfunction or loss in PD, and its chronic use is associated with a requirement for dose escalation and the development of adverse actions – including abnormal involuntary movements (AIMs) (i.e., levodopa-induced dyskinesia) (LID) [Rascol et al., 2000; Manson et al., 2012; Bjornestad et al., 2016]. In this light, other treatment options are required for PD that can be added to those currently available.
Long-acting glucagon-like peptide-1 (GLP-1) receptor agonists, also known as incretin mimetics, are approved, and widely used in the effective treatment of type 2 diabetes mellitus (T2DM). In the light of common underpinnings between T2DM and PD, clinically approved T2DM incretin mimetics are presently being evaluated in preclinical and clinical PD studies [Kopp et al., 2022]. The long-acting GLP-1 receptor agonist, Exenatide, has demonstrated efficacy in a phase 2 PD clinical trial [Athauda et al., 2017, and brain biomarkers associated with mitigation of insulin resistance correlated with Exenatide efficacy [Athauda et al., 2019]. Measures of dopaminergic mitochondrial function were not evaluated and there is little knowledge on whether they would respond positively to Exenatide treatment in preclinical studies.
The current service contract would provide such information and would provide a basis of whether biomarkers of mitochondrial function warrant measurement in human PD studies.
Focus of Contract: The focus of this contract is to measure markers of mitochondrial function by Seahorse Analyzer in a progressive mouse model of PD; specifically, the MitoPark mouse.
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:
Required services to be performed include:
1. Investigation: Seahorse evaluation of mitochondria from the brains of MitoPark mice with/without PT320-Exenatide treatment.
2. Quality control: Quality control – visual (microscopic) check of mitochondrial structure
3. Statistics: Statistical evaluations will be performed (ANOVA) followed by appropriate post hoc tests to support multiple comparisons. Use of appropriate software (GraphPad Prism 5.02, GraphPad Scientific, San Diego, CA, USA). A p-value <0.05 using a two-tailed test was considered significant.
4. Report: A report will be provided of the background, methods, and results (including statistical analyses and graphs/tables of major findings.
Additional details can be obtained from the key NIA scientist involved who will oversee the scientific basis of the project.
SPECIFIC REQUIREMENTS:
1. Animals. MitoPark mice have been generated on a C57BL6 background, in which the DA transporter (DAT) promoter is used to drive cre-recombinase expression, and these mice have been crossed with mice in which the Tfam gene has been loxP-flanked. These mice have been appropriately genotyped and used in approved Animal protocols across the world in prior successful preclinical PD studies [for example, Kuo et al., 2023].
2. Prior preclinical studies using the extended-release formulation of Exenatide – PT320 – have demonstrated its ability to mitigate/slow dopaminergic cell death and associated motor deficits in MitoPark PD mice [Wang et al., 2021].
3. The protocol of Wang et al., 2021 will be followed in MitoPark mice and PT320/Exenatide (0.6 mg/kg each two weeks, subcutaneously) will be administered and compared to Vehicle administered littermates. Seahorse Analyzer measures of oxygen consumption rate, extracellular acidification rate and energy metabolism will be made time-dependently.
4. Dosing will commence at 5 weeks age and continue until approx. 24 weeks of age. Evaluation of mitochondrial function will be undertaken some three times during the time course. A microscopic inspection of mitochondrial cell structure additionally will be performed to evaluate any obvious changes in gross structure.
Essential study Requirements from Contractor include:
1. Extensive background in preclinical studies involving the MitoPark mouse model of PD – must demonstrate with peer reviewed publications in Pub Med.
2. Contractor MUST have previous experience in studies involving Exenatide and the GLP-1 class of pharmacological drugs – must demonstrate with peer reviewed publications in Pub Med.
3. The Contractor’s Institution can take up to, but no more than, 10% of the contract as overhead charges.
LEVEL OF EFFORT: Senior scientist with background in neuroscience/neurodegeneration (with M.D., Ph.D. or both) with background in PD, Mitopark mice and knowledge of GLP-1 receptor agonist drugs
GOVERNMENT RESPONSIBILITIES: The Government will provide:
- PT320-Exenatide and
- Vehicle (and drug dose/schedule to be evaluated)
DELIVERY OR DELIVERABLES: Deliverables and Timeline (timeline = 12 months from award of contract)
One (1) research report providing a written overview of the data (tables and/or graphs/figures), statistical analyses, and evaluation of key results – as an electronic file
REPORTING REQUIREMENTS: One report is required – see deliverables, above.
The Contractor will have a short (approx. 15 min) once every month phone meeting with the key NIA scientist involved to highlight progress and define any problems that need input for resolution.
TRAVEL: Not applicable.
KEY PERSONNEL: Experienced neuroscientist with a strong background in PD research and neurodegeneration focused on drug development (that additionally meets the “Specific Requirements” – detailed above)
INFORMATION SYSTEM SECURITY PLAN: Not Applicable.
DATA RIGHTS: Data generated in relation to the contract will jointly belong to the Contractee (NIA/NIH) and Contractor and will be used to (i) support decisions whether to further develop the experimental drug PT320 and/or Exenatide as a new treatment strategy to mitigate PD, and (ii) will be published in the scientific literature and include Contractor as a coauthor.
SECTION 508 - Electronic and Information Technology Standards: Not Applicable.
PUBLICATIONS and PUBLICITY: The Contractor is not required to write or publish articles of data in relation to the SOW but is expected to provide input into any such publications.
CONFIDENTIALITY of INFORMATION: The Contractor shall keep confidential any documents/data provided by the Government that are not in the public domain and that are marked as ‘confidential’.
SUMMARY STATEMENT:
The Unique Entity Identifier (UEI), the Taxpayer Identification Number (TIN), certification of country of ownership, 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.
Quoter Terms and Conditions (To be completed by the Offeror):
- Period of Performance OR Delivery Date After Receipt of Order:
- Shipping Point (F.O.B. OR Destination):
- Payment Discount Terms:
- NIH BPA Number:
- SAM UEI No:
- Name of Company:
- Street Address, City, State, Zip code:
- Name of Person Authorized to Provide Quote:
- Telephone Number and Email Address of Person Authorized to Provide Quote:
ADDITIONAL TERMS AND CONDITIONS, PROVISIONS, AND REPRESENTATIONS
The FAR Clauses are incorporated by reference and are provided in full text at https://www.acquisition.gov/
- FAR Provision 52.212-1 Instructions to Offerors-Commercial Items (Nov 2021) is applicable to this solicitation.
- FAR Provision 52.212.2 Evaluation-Commercial Items (Nov 2021) is applicable to this solicitation. The Government will evaluate quotations or offers in accordance with FAR 13.106-2 and award a purchase order from this solicitation to the responsible offeror whose quote conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate quotes: Technical capability of the item offered to meet the Government requirement; Price; and Past performance [see FAR 13.106-2(b)(3)]
- FAR Provision 52.212-3, Offeror Representations and Certifications-Commercial Items (May 2022), is applicable to this solicitation.
- FAR Clause 52.212-4, Contract Terms and Conditions-Commercial Items (November 2021), is applicable to this solicitation.
- FAR Clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items (October 2022) is applicable to this solicitation.
- FAR Clause 52.227-14, Rights in Data - General
In addition, the following FAR provisions and clauses are applicable to this solicitation and incorporated by reference:
- 52.204-7 System for Award Management (Oct 2018),
- 52.204-13 System for Award Management Maintenance (Oct 2018),
- 52.204-16 Commercial and Government Entity Code Reporting (Aug 2020),
- 52.204-18 Commercial and Government Entity Code Maintenance (Aug 2020)
- HHSAR 352.239-73, Electronic and Information Technology Accessibility Notice (December 18, 2015)
- FAR 52.204-27, Prohibition on a ByteDance Covered Application (Jun 2023)
The following provisions and clauses apply to this acquisition and are incorporated as an attachment. Offerors MUST complete the provision at 52.204-24 and 52.204-26 and submit completed copies as separate documents with their quotation.
- FAR 52.204-24, Representation Regarding Certain Telecommunications and Video Surveillance Services or Equipment (Nov 2021)
- FAR 52.204-25, Prohibition on Contracting for Certain Telecommunications and Video Surveillance Services or Equipment (Nov 2021)
- FAR 52.204-26, Covered Telecommunications Equipment or Services-Representation (Oct 2020)
- NIH Invoice and Payment Provisions
All responses must be received by July 16, 2023 at 12 pm EST and must reference announcement/ solicitation number NIA-23-007828. Responses may be submitted electronically to Carla Blalock (Carla.blalock@nih.gov). Fax responses will not be accepted.
Interested parties may identify in writing their interest and capability in response to this requirement. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.
All responses must be received by closing date and must reference the announcement. Responses may be submitted electronically to the attention of the contract specialist. Fax responses will not be accepted.
All responsible sources may submit a bid, proposal, or quotation which shall be considered by the agency.