This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. NeuroAIDS is a common and debilitating consequence of HIV infection. No accepted therapies exist for neuroAIDS. The major toxicity of CNS HIV-1 infection for neurons is thought to be oxidant damage caused by HIV-1 proteins, mainly envelope (gp120) and Tat. Antioxidant gene delivery to the CNS may be an effective approach to treating not only neuroAIDS but other degenerative diseases that are thought to involve oxidant-related neurotoxicity. In vitro, human or rodent neurons exposed to HIV-1 gp120 or Tat undergo apoptosis, from which transduction with SV(SOD1) and/or SV(GPx1) is almost completely protective. In vivo, intraparenchymal or intracerebroventricular, inoculation of these vectors leads to long-term expression of these antioxidant enzymes and similarly protects from local challenge with recombinant HIV-1 gp120 and Tat. The ultimate goal to which this pilot project will lead is to study the use of recombinant Tag-deleted SV40-derived vectors (rSV40s) in CNS-directed gene delivery, to treat neuroAIDS other neurodegenerative diseases involving oxidant stress. The first step in this process, and the immediate goal of these studies is to confirm the ability of rSV40s to deliver expression of neuroprotective antioxidant enzymes and antilentiviral transgenes safely to the primate brain. In so doing, it is hoped to translate to a primate model the data generated with human and rodent CNS cells in tissue culture, and in vivo in rodent studies, documenting the transduction efficiency and safety of rSV40 gene delivery to the CNS. Data generated in this study will be used in ensuing NIH grant proposals to study and optimize rSV40 gene delivery of Cu/Zn superoxide dismutase (SOD1) and glutathione peroxidase (GPx1) to treat SIV-induced encephalopathy. NIH proposals to conduct clinical trials of gene therapy for neuroAIDS would follow. The first step, proposed here, is to document that these vectors deliver transgene expression to the primate CNS, durably and safely.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Primate Research Center Grants (P51)
Project #
5P51RR000164-48
Application #
7958682
Study Section
Special Emphasis Panel (ZRR1-CM-8 (01))
Project Start
2009-05-01
Project End
2010-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
48
Fiscal Year
2009
Total Cost
$36,334
Indirect Cost
Name
Tulane University
Department
Type
Other Domestic Higher Education
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Mahalingam, Ravi; Kaufer, Benedikt B; Ouwendijk, Werner J D et al. (2018) Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques. J Virol 92:
Kumar, Vinay; Mansfield, Joshua; Fan, Rong et al. (2018) miR-130a and miR-212 Disrupt the Intestinal Epithelial Barrier through Modulation of PPAR? and Occludin Expression in Chronic Simian Immunodeficiency Virus-Infected Rhesus Macaques. J Immunol 200:2677-2689
Parthasarathy, Geetha; Philipp, Mario T (2018) Intracellular TLR7 is activated in human oligodendrocytes in response to Borrelia burgdorferi exposure. Neurosci Lett 671:38-42
McNamara, Ryan P; Costantini, Lindsey M; Myers, T Alix et al. (2018) Nef Secretion into Extracellular Vesicles or Exosomes Is Conserved across Human and Simian Immunodeficiency Viruses. MBio 9:
Calenda, Giulia; Villegas, Guillermo; Barnable, Patrick et al. (2017) MZC Gel Inhibits SHIV-RT and HSV-2 in Macaque Vaginal Mucosa and SHIV-RT in Rectal Mucosa. J Acquir Immune Defic Syndr 74:e67-e74
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Yi, Fei; Guo, Jia; Dabbagh, Deemah et al. (2017) Discovery of Novel Small-Molecule Inhibitors of LIM Domain Kinase for Inhibiting HIV-1. J Virol 91:
Jorgensen, Matthew J; Lambert, Kelsey R; Breaux, Sarah D et al. (2017) Pair housing of Vervets/African Green Monkeys for biomedical research. Am J Primatol 79:1-10
Ramesh, Geeta; Martinez, Alejandra N; Martin, Dale S et al. (2017) Effects of dexamethasone and meloxicam on Borrelia burgdorferi-induced inflammation in glial and neuronal cells of the central nervous system. J Neuroinflammation 14:28
Parthasarathy, Geetha; Philipp, Mario T (2017) Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi. J Neuroinflammation 14:110

Showing the most recent 10 out of 352 publications