SOLICITATION NOTICE
A -- Identification and Characterization of Novel Therapeutics for the Treatment and Prevention of Epilepsy and Neuroprotectants as Counter Measures (CM) to Chemical Threats
- Notice Date
- 11/9/2010
- Notice Type
- Presolicitation
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 6001 Executive Boulevard, Neuroscience Center, Suite 3287, MSC 9531, Bethesda, Maryland, 20892-9531
- ZIP Code
- 20892-9531
- Solicitation Number
- NIH-NINDS-10-04
- Archive Date
- 1/8/2011
- Point of Contact
- Helene C Braun, Phone: 301 496-1813
- E-Mail Address
-
hb106s@nih.gov
(hb106s@nih.gov)
- Small Business Set-Aside
- N/A
- Description
- The National Institute of Neurological Disorders and Stroke (NINDS) intends to negotiate on a non-competitive basis the continuation of a contract with the University of Utah for the "Identification and Characterization of novel Therapeutics for the Treatment and Prevention of Epilepsy and Neuroprotectants as Counter Measures (CM) to Chemical Threats." The primary continuing goals of the contract are to evaluate novel compounds as potential: anticonvulsants, neuroprotectants, treatments for neuropathic pain and as therapies to combat exposure to chemical nerve agents. The Anticonvulsant Screening Program (ASP) conducts extensive testing to facilitate drug discovery and translational activities aimed at identifying, optimizing and translating such discoveries into therapeutics for affected patients. Active compounds are identified and tested through a series of pharmacodynamic and pharmacokinetic evaluations (both in vivo and in vitro tests) that help define anticonvulsant or related disease profiles of candidate compounds. Test parameters include but are not limited to: Baseline assessments of anti-seizure activity, neurotoxicity, effects on hepatic microsomal metabolizing enzymes, pharmacodynamic interactions, brain slice survival rates and chronic EEG monitoring. These efforts have been carried out under the contract mechanism since 1975 with the University of Utah. Approximately 700 compounds are evaluated annually for anticonvulsant and related activities. Overall testing requirements include the following: 1) Anticonvulsant Identification: evaluation of anticonvulsant activity and associated neurotoxicity in mice, following intraperitoneal administration using the 6 Hz induced focal seizures; 2) Compounds displaying significant activity may be further evaluated with subsequent quantitation using the supramaximal electroshock seizure pattern test (MES), the subcutaneous pentylenetetrazol (sc Met) threshold test and the rotorod test. Those compounds possessing significant anticonvulsant activity in mice may also be evaluated in rats using similar models but via different routes of administration. Both activity and toxicity shall be quantitated at previously determined time of peak effects; 3) Pharmacologic Differentiation - Anticonvulsant profiles are developed wherein the efficacy will be compared with that of the prototype drugs. As part of this process, the efficacy is quantitated using seizures induced by bicuculline and picrotoxin. 4) Anticonvulsant profiles of candidate anticonvulsant compounds are also developed in rats by the rapid hippocampal-kindling model of complex partial seizures or the corneal kindled mouse model. Candidate substances are evaluated for their ability to block the expression of kindled seizures in either the rapid hippocampal kindling or the corneal kindled mode. A number of active candidates shall be tested and quantitated for their ability to block the acquisition of kindled seizures induced by rapid hippocampal stimulation. 5) Profiles for selected test substances will include a genetically susceptible model of reflex epilepsy; 6) Proconvulsant Potential - The endpoint being length of time taken for evidence of seizure activity following the infusion of pentylenetetrazol into the tail vein of mice; 7) Drug Interaction Studies - The metabolic potential for drug-drug interactions are determined using human liver microsomes. The potential to inhibit a battery of the major P-450 human liver isozymes are determined along with comparative assessment of the standard available anticonvulsants; 8) Metabolic gene induction studies; 9) Lamotrigine Resistant Kindled Rat Test - Animals will be kindled according to the procedure described by Postma et al. (2000) with seizures scored according to a Racine Scale (Racine, 1972). Seizure scores and afterdischarge durations will be recorded for each animal; 10) AED Modulation of Axonal Neurotransmission - this will be assessed via at least two tests: Partial Ligation of the Sciatic Nerve and the Formalin Test which are used to determine efficacy of an investigational AED against the acute and chronic hyper-responsive neuronal discharges following activation of peripheral nerve fibers. Other models of pain used are the Chung, tail flick and the carragheenan. 11) Slice electrophysiology studies and 24 hour EEG recordings are performed on a select number of candidates. 12) Morris Water Maze as a study of learning and memory along with the forced swim test; 13) Pilocarpine induced SE prevention model. Compounds will be assessed for pharmacological evaluation of potential activity to halt pilocarpine-induced convulsive status epilepticus (SE); 14) Benzodiazepine-resistant status epilepticus: Nerve-agent exposure causes convulsive status epilepticus (SE) that becomes resistant to benzodiazepine therapy over time, it is the goal of the NINDS to find therapeutic agents that block pilocarpine-induced electrographically monitored seizures at times when benzodiazepines (e.g. diazepam) no longer block electrographic SE. 15) Finally, comprehensive summary reports are required for the best candidates (approximately 12 per yr.) that provide methods, detailed results, comparative assessments, discussions and conclusions. During the last 35 years, the University of Utah has been able to successfully adopt specialized techniques, methods of evaluation, model development and accumulation of extensive pharmacodynamic and pharmacokinetic profiles for all the current therapeutic agents and most new investigational drugs. This accumulation of data and experiences is the basis by which all new test compounds are pharmacologically compared. The NINDS believes that the University of Utah is the only known source to collectively perform these comprehensive evaluations by virtue of their experience, demonstrated expertise, availability of required staff, laboratory and animal facilities and requisite trained personnel and resources. The NINDS rigorous requirements for consistency, compatibility and validation of data derived from these screening procedures is paramount to the success of this program. Inability to produce compatible evaluation results to our existing data base would lead to delays in screening new compounds and incurrence of duplicate costs, both of which would be unacceptable to the Government and would disrupt the continuity of this work. Organizations that believe they have the qualifications and capabilities necessary to undertake this work should submit complete documentation of staffing, facilities, and methodologies currently in place to the Contracting Officer at the above address within 45 days from the date of this announcement. An organization must have an ongoing program, available staff possessing substantial experience in conducting the required tests. They must also have the equipment, space and infrastructure in place to carry out the work described above. All responsible sources may submit a bid, proposal, quotation or capability statement which shall be considered by the NINDS. The determination by the Government not to compete the new contract based upon responses to this notice is solely within the discretion of the Government. Authority: 45 U.S.C. 253©(1), as set forth in FAR 6.302-1. This is not a formal solicitation or an announcement that a Request for Proposals (RFP) is available.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NINDS/NIH-NINDS-10-04/listing.html)
- Place of Performance
- Address: University of Utah, Salt Lake City, Utah, 84112, United States
- Zip Code: 84112
- Zip Code: 84112
- Record
- SN02324781-W 20101111/101109234105-5322b928fd8760e280babe141b0e689f (fbodaily.com)
- Source
-
FedBizOpps Link to This Notice
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