Inactive

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 I... 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: Histochemical Behavioral 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. The dose of PT320 will be 0.6 mg/kg, subcutaneously once every 2 weeks. 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 <0.05 using a two-tailed test was considered significant. 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

Inactive

Description: This is a Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availabilit... Description: This is a Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential requirement. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. Background: Preclinical studies in mice to evaluate the repurposing of an approved type 2 diabetes mellitus drug, Exenatide, for the treatment of Parkinson’s disease - for which there is no current pharmacological treatment that slows disease progression. The evaluation of preclinical efficacy of a new treatment strategy for Parkinson’s disease to evaluate Exenatide on disease progression Purpose and Objectives: This contract is to 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. Project 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 Specifics outlined below: Specifics: Exenatide studies. Exenatide will be provided by the Government 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. (i) The dose of PT320 will be 0.6 mg/kg, subcutaneously once every 2 weeks. (ii) 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 shall 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 shall 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 during 1 hour were taken as distance traveled. Cylinder test. The cylinder test shall 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 shall 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 shall 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 shall 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 from Dr. Greig TGB/NIA/NIH). Longitudinal imaging studies shall 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 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 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 <0.05 using a two-tailed test was considered significant. Additional Requirements: ESSENTIAL study Requirements from Contractor Extensive background in preclinical studies involving the MitoPark mouse model of PD – must demonstrate with peer reviewed publications in Pub Med. Contractor MUST have previous experience in the use and handling of Exenatide and GLP-1 class of pharmacological drugs – must demonstrate with peer reviewed publications in Pub Med Anticipated period of performance: The period of performance is 12 months following the award of the contract. Capability statement /information sought. Respondents must provide, as part of their responses, a capability statement that clearly identifies their ability to provide the service described above. Respondents must also include information regarding their: (a) staff expertise, including their availability, experience, and formal and other training; (b) current in-house capability and capacity to perform the work; (c) prior completed projects of similar nature; (d) corporate experience and management capability; and (e) examples of prior completed Government contracts, references, and other related information; The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2” x 11” paper size, with 1” top, bottom, left and right margins, and with single or double spacing. The information submitted must be in an outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein. A cover page and an executive summary may be included but is not required. The response is limited to ten (10) page limit. The 10-page limit does not include the cover page, executive summary, or references, if requested. The response must include the respondents’ technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted. The response must be submitted to Diedra Prophet at e-mail address Diedra.Prophet@nih.gov and Karen Mahon at e-mail address Karen.Mahon@nih.gov. The response must be received on or before July 14, 2020, at 2:00 pm Eastern Time. “Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).