Inactive

There is an unmet medical need for safer, less addictive, and more effective solutions for chronic pain management. Current methods involving the prescription of opioids to patients with chronic pain ... There is an unmet medical need for safer, less addictive, and more effective solutions for chronic pain management. Current methods involving the prescription of opioids to patients with chronic pain has led to an unsustainable and deadly epidemic of addiction. Alternative methods of treating pain are therefore required to mitigate opioid substance abuse and addiction. The object of this project is to establish the efficacy of the nanoparticle formulation by replicating previous research investigations that compared the nanoparticle formulation to a free drug formulation. The scope of this project is for the contractor to execute the neuropathic pain model in adult rodents, treat animals with the compounds, and evaluate drug efficacy at different doses by measuring evoked and spontaneous pain. Specifically, the contractor shall perform a Mouse SNS (Sural Nerve Spared) model of neuropathic pain with use of von Frey Hairs (vFH) for assessment of mechanical allodynia. See attached Request for Quotations, Statement of Work, and other attachments for complete requirement details.

Inactive

Description This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: ... Description This is a Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. 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. Please note that to qualify as an eligible small business for purposes of a small business set-aside, at least 50% of the cost of contract performance incurred for personnel must be expended for employees of the small business awardee (see FAR 52.219-14 Limitations on Subcontracting). Background There is an unmet medical need for safer, less addictive, and more effective solutions for chronic pain management. Current methods involving the prescription of opioids to patients with chronic pain has led to an unsustainable and deadly epidemic of addiction. Alternative methods of treating pain are therefore required to mitigate opioid substance abuse and addiction. In the body, pain is transmitted through the nervous system via the activity of G-protein coupled receptors (GPCRs) found on neurons in the central and peripheral nervous systems including the brain and spinal cord. GPCRs can function at the surface of these cells, or in internalized compartments called endosomes. These endosomal GPCRs (eGPCRs) have recently been implicated in the transmission of pain, or nociception, and include the substance P neurokinin 1 receptor (NK1R) and calcitonin gene related peptide (CGRP) calcitonin- like receptor (CLR), which are co-expressed by a population of spinal neurons, and protease activated receptor 2 (PAR2), which is expressed by some nociceptors. By specifically targeting eGPCRs, it is hypothesized that superior pain relief can be achieved via particular endosomal targets which have been demonstrated to be responsible for ongoing signaling in chronic pain and which, due to their compartmentalized location, may not have been optimally targeted by previous clinical agents. Selective delivery of small molecule antagonists can be achieved with encapsulation into an acid labile nanoparticle that breaks down inside the acidic compartment of the endosome to release the antagonist, specifically targeting the eGPCR signaling of the nociceptive transmission pathway. The FDA-approved small molecule aprepitant (AP) is encapsulated into DIPMA polymers and has been shown to target the endosomal NK1R signaling of the spinal cord dorsal horn neurons after intrathecal (i.t.) administration. This is a non-opioid treatment for chronic pain that could potentially bring relief to patients as a substitute for potentially harmful and habit-forming opioids. Purpose and Objectives The objective of this project is to establish the efficacy of the nanoparticle formulation by replicating previous research investigations that compared the nanoparticle formulation to a free drug formulation. This requirement replicates work by Prof Nigel Bunnett (NYU) et al in this model shared with NCATS. Project Requirements The scope of this project is for the contractor to execute the neuropathic pain model in adult rodents, treat animals with the compounds, and evaluate drug efficacy at different doses by measuring evoked and spontaneous pain. The contractor shall perform a Mouse SNS (Sural Nerve Spared) model of neuropathic pain with use of von Frey Hairs (vFH) for assessment of mechanical allodynia. The specific methods are listed below. Methods: Surgery = SNS = Sural spared, Tibial transected, Peroneal transected Mouse strain C57BL/6 Drug delivery intrathecally (i.t.) by direct injection and not via catheter: DIPMA AP (nanoparticles loaded with aprepitant) or free aprepitant to be administered by direct i.t. injection at 10 days post-SNI (5 uL volume used in mouse) to the L4/5 region of the spinal cord vFH as readout of mechanical allodynia to be measured every 30 min for at least 5 hours. DIPMA NPs will be freshly supplied for these studies and must be used within 4 weeks of the date of formulation First ‘gating’ study must be to demonstrate the efficacy of a high concentration of free aprepitant (e.g. 1 uM), dosed by direct intrathecal injection, prior to evaluating DIPMA nanoparticles. This is considered to be an essential positive control for utility of model for NK1 pharmacology and successful i.t. delivery in line with the extensive NK1 target literature. Test dose of DIPMA AP: 5uL volume of a 500 nM DIPMA AP solution (can also extend to 100 / 300 /1000 nM for dose-response purposes) Comparator dose of free AP: 5uL volume of a 500 nM AP solution (can also extend for dose-response and differentiation purposes e.g. up to 1uM) Study Protocol: The contractor will draft a study that will be reviewed and approved by the Government. This protocol must be approved by the Government prior to the beginning of any research activity. Deliverables: The contractor shall provide a final report that includes the raw data, data analyses, a summation of the work performed, and results obtained. This report shall contain, but not be limited to, the following information: Material and Methods, Animals, Doses treated, Test materials, Experimental design, Statistical analysis, Study results, Conclusions, Tables, Figures, and a Copy of all raw data. This report shall be in sufficient detail, as determined by the Government, to comprehensively describe the achieved results. Government Responsibilities: The Government will provide sufficient quantities of the lead compound for the contractor to accomplish the necessary work. Contract Type and Anticipated Period of Performance The Government anticipates awarding a fixed-price purchase order with a period of performance of one year. Required Information Responses must include: 1. Information about the respondent’s current in-house capability and capacity to perform the work. If subcontracting is anticipated, responses should note the extent of subcontracting and anticipated subcontractors. 2. Information about the respondent’s prior completed projects of a similar nature. 3. Whether or not the respondent has an active Assurance from the NIH Office of Laboratory Animal Welfare (OLAW), and if so, the Assurance Number. Responses must also include (1) DUNS number; (2) organization name; (3) organization address; (4) point of contact; (5) point of contact title, address, telephone, and email address; and (6) size and type of business (e.g., 8(a), HUBZone, etc.) pursuant the applicable NAICS code. Submission Instructions and Due Date Responses must be submitted electronically to Kimberly Espinosa, Contract Specialist, at kimberly.espinosa@nih.gov. Responses must be received on or before Thursday, April 15, 2021, at 3:00pm 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 Beta.SAM.gov. 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).