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FBO DAILY - FEDBIZOPPS ISSUE OF JULY 12, 2018 FBO #6075
SOURCES SOUGHT

B -- Evaluation of phenserine tartrate and a Pomalidomide analog in a mouse model of moderate traumatic brain injury - Statement of Work

Notice Date

7/10/2018
 

Notice Type

Sources Sought
 

NAICS

541990 — All Other Professional, Scientific, and Technical Services
 

Contracting Office

Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, 6001 Executive Boulevard, Room 4211, MSC 9559, Bethesda, Maryland, 20892-9559, United States
 

ZIP Code

20892-9559
 

Solicitation Number

NIHDA201800327
 

Archive Date

7/31/2018
 

Point of Contact

Jon J Gottschalk, Phone: 3014439456, Yvette Brown, Phone: 301-443-8402
 

E-Mail Address

jon.gottschalk@nih.gov, yvette.brown@nih.gov
(jon.gottschalk@nih.gov, yvette.brown@nih.gov)
 

Small Business Set-Aside

N/A
 

Description

Statement of Work Federal Business Opportunities (FBO) SOURCES SOUGHT NOTICE 1.Solicitation Number: NIHDA201800327 2.Title: Evaluation of phenserine tartrate and a Pomalidomide analog in a mouse model of moderate traumatic brain injury 3.Classification Code: B 4.NAICS Code: 541990 5.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: Currently, there are no FDA approved drugs for the pharmacological treatment of traumatic brain injury (TBI), although some 10 to 42 million people worldwide, including more than 1.7 million Americans, experience a TBI annually [1]. Alarmingly, TBI is surpassing many common diseases as a major cause of death and disability [2] (30.5%). Of further concern, there is an increased mortality in the elderly and a worse functional outcome following lower initial injury severity [3]. In addition to acute effects (cognitive loss, depression, sleep disorders, anxiety, etc.), TBI triggers a pathological cascade that can lead to early dementia onset [4,5] and is one of the most powerful risk factors for the development of Alzheimer's disease and related disorders [6]. By far the majority of TBIs are mild to moderate in nature and account for 80-95% of cases, with severe TBI comprising the remainder. With increases in survival rate following initial injury, TBI can result in substantial and lifelong cognitive, physical, and behavioral impairments that require long-term access to health care and disability services [7]. TBI-associated brain damage in generally categorized into two primary phases. First, an initial phase of primary damage occurs at the moment of insult. This includes contusion and laceration, diffuse axonal injury and intracranial hemorrhage, generally causing instantaneous (necrotic) cell death. This is followed by a longer second phase involving biological processes initiated at the time of injury that may continue over a far greater duration - driven by ischemia, neuroinflammation, glutamate toxicity, astrocyte reactivity, axonal shearing and apoptosis [8-11]. Such secondary brain injury may be reversible; depending on the time-dependent biological processes that drive this extended secondary phase and how quickly and effectively these can be mitigated. Preclinical studies of the NIA experimental drug phenserine tartrate (PhenT) as well Pomalidomide (Pom) analogs can mitigate mild TBI in a well characterized mouse model [12,13]. These agents appear to have a broad spectrum of pharmacological activities of potential value for the treatment of mTBI as well as long term neurodegenerative disorders [14]. These include lowering the synthesis of amyloid precursor protein (APP) and alpha-synuclein (α-syn), proteins of consequence in the pathology of AD and Parkinson's disease, respectively. In addition, PhenT possesses anti-inflammatory properties [13], also a phenomenon of significance in TBI [15], as well as an array of trophic and, importantly, anti-apoptotic actions [12,16]. The focus of this SOW is to critically evaluate these agents in a well characterized mouse model of moderate TBI. This is important as no single animal model is predictive of activity in humans, and hence the demonstration of efficacy across animal TBI models in important (17) Purpose and Objectives: Preclinical studies in mice to evaluate two experimental drugs for efficacy in a controlled cortical impact model of moderate traumatic brain injury. The objective of this contract is to assess whether or not either of the two experimental drugs warrants evaluation as a new treatment strategy for moderate traumatic brain injury - for which there is no current pharmacological treatment. Project requirements: Histochemical, behavioral and biochemical analysis of TBI mice after treatment with phenserine tartrate and a Pomalidomide analog. Six groups of mice, 30 animals per group (15 males and 15 females), will be exposed to telencephalic CCI or sham injury followed by administration within 5 h after injury of either (1) vehicle, (2) phenserine tartrate, or (3) a Pomalidomide analog. Each group of 30 will be subdivided into two groups for assessment of behavior and biochemical changes in 18 and 12 animals, respectively. The phenserine dose administered will be 2.5 mg/k BID x 5 days after injury and the Pomalidomide analog dose will be 28 mg/kg once daily x 5 days. Both of these experimental drugs will be provided by Dr. Nigel H. Greig, NIA, NIH, at no cost to the contract. Since hypothermia is neuroprotective, monitoring and regulating body temperature during and after CCI surgery and drug administration will be undertaken to obviate this potential caveat. Although CCI produces a relatively stable and reproducible injury, righting reflex time will be measured postoperatively after CCI to further document comparability between the various treatment groups. Behavior Assay (18 animals per group): Animals will undergo motor testing and behavioral testing as detailed below at baseline. After CCI or sham injury, animals will undergo motor and behavioral testing again at 24 h after injury (9 animals) or at 7 days after injury (9 animals), followed by histological analysis using cresyl violet and fluoroJade C (FJC) staining. Motor Behavior: Evaluations will consist of a modified neurological severity score (mNSS) assessment, a tactile adhesive removal test, an elevated body swing test and a beam walk test. All will be performed by an observer blinded to the experimental groups. Overall motor activity will be measured in automated chambers. To compare neurological deficit severity in TBI mice, a mNSS (a composite of motor, sensory, reflex and balance tests) will be performed. One point is scored for inability to perform the test or for the lack of a tested reflex; thus, the higher the score, the more severe the injury. Neurological function is graded on a scale of 0-18 (normal score, 0; maximal deficit score, 18). A tactile removal test will be used to evaluate somatosensory function. In this test, two small adhesive-backed stickers are used as bilateral tactile stimuli that are placed on the distal-radial region on the wrist of each forelimb. Mice will be pre-trained daily for 3 days before CCI. The time required (not to exceed 180 s) for the mouse to remove the sticker from the forelimb will be recorded. Cognitive Behavior: The Novel Object Recognition (NOR) and Y-Maze paradigms will be used. The NOR paradigm will evaluate recognition memory in mice. This task is based on the innate tendency of rodents to explore new objects within their environment. A discrimination preference index is calculated as follows: (time spent near the new object minus time spent near the old object) / (time spent near the new object plus time spent near the old object). After each session, the objects and arenas will be thoroughly cleaned with 70% ethanol to prevent odor recognition. The Y maze paradigm will assess rodent spatial memory based upon observing the preference of the animal for a ‘new' location over a ‘familiar' location on two separate occasions. The time each mouse spends within the arms is recorded and used to generate a preference index, as initially described by Dix and Aggleton. Likewise, the maze will be cleaned using a 70% ethanol solution and dried in order to prevent any olfactory recognition between trials. Histology evaluation Cresyl violet and FJC staining will be used to assess contusion volume and neuronal degeneration, respectively. FJC (Biosensis, TR-100-FJ) binds selectively to degenerating neuronal cells. All sections will be observed and photographed under a fluorescence microscope with a blue (450-490 nm) excitation light with blinded observers and unbiased stereology (Microbright). Cresyl violet will be used to measure contusion volume, by staining sections followed by digitization and analysis using a 1× objective and computer image analysis system. Contusion area will be calculated from all images of cresyl violet-stained sections that contain contused brain. Hemisphere tissue loss will be expressed as a percent calculated by [(contralateral minus ipsilateral hemispheric volumes) / contralateral hemispheric volume) × 100%]. Biochemistry and Immunocytochemistry Assay (12 animals per group): Animals will be euthanized 8 h after injury for biochemical and immunofluorescence markers. Both the injured and non-injured sides will be used for these studies in both CCI and sham animals. Immunocytochemistry: Sections will be incubated with the appropriate primary antibodies, either mouse monoclonal anti-NeuN antibody (Millpore; 1:500, NeuN is a neuronal marker)/ anti-p53 antibody (GeneTex; 1:500) / anti-annexin V antibody (Abcam ; 1:500) / anti-p-p53 antibody (Cell signaling; 1:1000) / or anti-PUMA antibody (Abcam; 1:200) at 4°C overnight and with secondary antibodies (Alexa Fluor® 488 goat anti-rabbit IgG (1:200, Jackson ImmunoResearch, West Grove, PA); Alexa Fluor® 594 anti-mouse IgG (1:200 dilution, Jackson ImmunoResearch, West Grove, PA)). The numbers of NeuN-, p53-, annexin V-, p-p53-, and PUMA-positive cells are counted in 5 randomly selected fields by means of SPOT image analysis software using blinded observers and unbiased stereology (MBF biosystem). Statistical Analysis Evaluation of data will use T-tests for simple two group comparisons, ANOVA for multiple group comparisons with Tukey post-hoc analysis, and appropriate tests for nonparametric data as needed. The Bonferroni correction will be used for serial comparisons over time. In cases where the time course of changes is important, as in the current proposal, nonlinear regression analysis will be applied. For a two-sided test of a null hypothesis of equality in mean values with Type I error of 0.05, power = 0.85 for an effect size of 1.35 (estimated based on results of our previous studies), this study will require a minimum of 17 animals per group to detect the targeted outcome, so the proposed sample size should be sufficient. Numbers for all experiments will be subject to modification as more data on variance is obtained. Anticipated period of performance: 6 months following the date of award. Other important considerations: ESSENTIAL study Requirements from Contractor (i)Extensive background in preclinical TBI rodent studies to evaluate the efficacy of experimental drugs. (ii)Contractor MUST have previous experience in the use and handling of Phenserine tartrate in preclinical studies to be familiar with its pharmacological actions (iii)Contractor MUST have previous experience in the use and handling of Pomalidomide and/or analogs thereof in preclinical studies to be familiar with its pharmacological actions (iv)Contractor MUST have an active and institutionally approved animal protocol to allow the use of CCI moderate TBI in a mouse (v)The Contractor's Institution can take up to BUT NO MORE THAN 10% of the contract as overhead charges. Capability statement /information sought. Contractors that believe they possess the ability to provide the requirement should submit documentation of their ability to meet each of the project requirements to the Contract Specialist. The response should directly and specifically state in the, capabilities statement, which project requirements you can supply. Contractors must also provide their Company Name, DUNS Number, Physical 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 must be in and 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 Jon Gottschalk, at e-mail address jon.gottschalk@nih.gov The response must be received on or before 12:00, pm, Eastern Time on Monday July 16, 2018. 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).
 

Web Link

FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIDA-01/NIHDA201800327/listing.html)
 

Place of Performance

Address: 251 Bayview Blvd, Baltimore, Maryland, 21224, United States

Zip Code: 21224
 

Record

SN04984652-W 20180712/180710230930-ce7f216e408f987a5907ddcaa660ba7f (fbodaily.com)
 

Source

FedBizOpps Link to This Notice
(may not be valid after Archive Date)

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