SOLICITATION NOTICE
B -- Professional Service to support the NIMH's Pathogenesis of NeuroAIDS
- Notice Date
- 8/20/2010
- Notice Type
- Presolicitation
- 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, Station Support/Simplified Acquisitions, 31 Center Drive, Room 1B59, Bethesda, Maryland, 20892
- ZIP Code
- 20892
- Solicitation Number
- NOI-1719938
- Archive Date
- 9/18/2010
- Point of Contact
- Liem T Nguyen, Phone: 3014358780
- E-Mail Address
-
ln18x@nih.gov
(ln18x@nih.gov)
- Small Business Set-Aside
- N/A
- Description
- The National Institute of Health (NIH), National Institute on Drug Abuse (NIDA) Office of Acquisitions, Station Support Simplified Acquisitions Branch on behalf of the National Institute of Mental Health (NIMH) intends to negotiate and award a purchase order on a non-competitive basis with Dr. Andrew A. Lackner, Tulane University Health Science Center, 18703 Three Rivers Road, Covington, LA for professional service in Pathogenesis of NeuroAIDS. The Division of AIDS Research at the National Institute of Mental Health (NIMH) has supported the acceleration of basic and translational scientific discoveries with a plan to advance drug therapeutics for HIV-Associated Neurocognitive Disorders (HAND) through a program entitled, Novel NeuroAIDS Therapeutics: Integrated Preclinical/Clinical Program (IPCP). Dr. Steven D. Douglas was supported by the IPCP entitled "Neurokinin-1R (Substance-P Receptor) Antagonists for HIV Therapy". As part of this IPCP translational research program Dr. Douglas studied the effects of the neurokinin-1 pathway, including the neurokinin-1 receptor (NK1R), its agonist Substance P (SP) and its antagonists with respect to HIV infection, inflammation, NeuroAIDS pathogenesis, and treatment. Important milestones achieved were the demonstration that NK1R antagonists have anti-HIV activity on human macrophages when purified from peripheral blood and tested in vitro. The data indicate that the anti-HIV activity of aprepitant is mediated through down-regulation of the CCR5 chemokine receptor, which is found on macrophages and is known to serve as an entry point for HIV. In addition, the NK1R agonist, SP, was shown to be a pro-inflammatory mediator. Collectively, the research indicates that inhibition of the neurokinin-1 pathway at the level of the receptor on monocytes/macrophages may serve as a means to inhibit HIV infection and regulate immunomodulatory events. An important element of Dr. Douglas's program project was to confirm some of his in vitro findings using an animal model. A SIV macaque model was used for his studies and was carried out in collaboration with Dr. Andrew Lackner (Tulane National Primate Research Center, New Orleans, LA). Dr. Lackner is an international expert in studying SIV neuropathogenesis. Dr. Lackner contributed his expertise with the SIV macaque model of AIDS to discern that both SP and its receptor, the NK1R, are localized to brain lesions of SIV encephalitis (IPCP Project 3). The macrophage and multinucleated cells in the lesions were also shown to express NK1R. In addition, SP expression was shown to be altered in macaques infected with SIV. The effects of aprepitant in normal and SIV-infected macaques were also ascertained by Dr. Lackner to determine the pharmacokinetics, immunologic & behaviorial response, safety, and the potential efficacy. The anti-viral effects of aprepitant were also studied and a one log reduction in peripheral viral load was detected. Dr. Lackner's research modeling viral infection in macaques provided preclinical support for the Phase 1b human clinical trial which was later implemented by Dr. Douglas. Dr. Lackner has also collected SIV macaque samples of plasma, CSF, and brain tissue which have been stored frozen for any future studies. A recent meeting of the Scientific Advisory Panel (SAP) for Dr. Douglas's program project was convened in April 2010, to review the in vitro and in vivo findings generated from the study. The panel felt that additional studies were needed to further clarify some of the findings presented. This acquisition is proposed to acquire the support to complete the studies suggested by the SAP since the NIMH program project award to Dr. Douglas has ended. A key finding that needed further work was that aprepitant (125 mg/day) successfully decreased the plasma viral load by one log in macaques after three months of treatment. The SAP felt that it would be critical to find out if viral load in the brain was being impacted by aprepitant since this could have major impact on SIV neuropathogenesis. In addition, the SAP felt that it was important to further examine the effect on aprepitant on immune activation in the CNS to determine if it alters the cytokine and chemokine profiles known to impact lymphocyte trafficking into the brain. Outlined below are the details on completing the studies examining antiviral and immunomodulatory effects of aprepitant with the SIV macaque samples previously collected by Dr. Lackner. Scope of Work: Tulane University Health Science Center and Dr. Lackner will conduct additional experiments on the SIV macaque samples from plasma and CSF previously collected and stored frozen to ascertain the effect of aprepitant in the brain. This research effort will determine whether the anti-viral effect of aprepitant in the plasma extends to the cerebrospinal fluid. These will include: 1. Measurement of viral load in 36 macaque samples that have not been completed, including plasma and CSF from SIV-infected and SIV-infected, aprepitant-treated macaques. 2. If differences appear to exist, statistical analyses should be completed at each point. In addition, Tulane University Health Science Center and Dr. Lackner will perform brain viral load analysis on 4 different brain regions (blocks) from each of 6 animals. The quantitative RT-PCR RNA extractions and analyses in aprepitant-treated animals were not included in the IPCP award. These will include: 3. One control uninfected animal, 4. Two SIV-infected animals, and 5. Two SIV-infected animals treated with aprepitant. Finally, Tulane University Health Science Center and Dr. Lackner will test the hypothesis that aprepitant reduces immune activation and reduces expression of NK1R and substance P in the brain of SIV infected Rhesus macaques treated with aprepitant compared to untreated Rhesus macaques with SIV infection. These studies will rigorously identify the brain cell types that express NK1R and determine whether those cells are infected with SIV. These studies will aid in the determination of whether aprepitant is able to reverse the pathology in the SIV macaque model. These will include: 6. Use in situ hybridization, immunohistochemistry and multi-label confocal microscopy to compare NK1R expression with multiple labels for SIV, the immune activation marker CD163, GFAP and NSE to rigorously identify the cell types expressing NK1R and determine if those cells are infected with SIV; 7. Assay three different brain regions (blocks) from each of 5 animals; 8. Each brain region (block) will have three different multilabel combinations (NK1R/SIV/CD163, and NK1R/SIV/GFAP, and finally NK1R/SIV/NSE; 9. Immunohistochemistry will be used to ascertain the location of Substance P in each brain region tested by confocal microscopy; 10. 80 assays will be completed. As noted above, the Tulane University Health Science Center is host to the National Primate Research Center and Dr. Lackner is the Center Director and Professor of Microbiology, Immunology and Pathology. Over the last 20 years Dr. Lackner has gained extensive expertise in evaluating the immunopathogenesis and neuropathogenesis of AIDS associated retroviruses in nonhuman primates including SIV. He is a leader in the use of Rhesus macaque SIV model. Dr. Lackner has a team of scientists with expertise in the examination of the localization of agents in situ, the co-localization of agents and cellular markers, and the use of confocal microscopy and image analysis in four channels. All samples to be analyzed for this contract were collected as part of Project 3 of the Douglas IPCP and are currently held in Dr. Lackner's laboratory. It is determined that Dr. Lackner and the Tulane University is the best known source to successfully perform the requirement. There is no other available source in the field with the knowledge and expertise needed to perform the requirement. No other source will satisfy the agency's requirement. The period of performance of this acquisition is for five (5) months from the date of award. Place of performance is in Bethesda, Maryland. No solicitation package will be issued. This notice of intent is not a request for competitive quotations; however, interested party who can meet the above requirement may submit a statement of capabilities on or before 11:00 AM local time September 3, 2010 to Liem T Nguyen, ln18x@nih.gov. All information furnished must be in writing and must contain material in sufficient detail to allow the government to determine if the party can perform the requirement. Please reference announcement number NOI-1719938 on all correspondence. A determination by the Government not to compete this proposed acquisition based upon responses to this notice is solely within the discretion of the Government. Information received will be considered solely for the purpose of determining whether to conduct a competitive procurement. In order to receive an award, contractors must be registered in and have valid certifications in the Central Contractor Registration (CCR), www.ccr.gov and the Online Representations and Certifications Application (ORCA) www.orca.bpn.gov.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIDA-2/NOI-1719938/listing.html)
- Place of Performance
- Address: Bethesda, Maryland, 20892, United States
- Zip Code: 20892
- Zip Code: 20892
- Record
- SN02248750-W 20100822/100820235126-fef0a8b58e9fc82e27a2263e645aa882 (fbodaily.com)
- Source
-
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