JHU NIMH Center for novel therapeutics for HIV-associated cognitive disorders. HIV-associated neurocognitive disorders (HAND) remain very prevalent, even among aviremic HIV+ individuals who treated with highly active antiretroviral treatments. HIV-related neuroscience research at Johns Hopkins University has focused on this challenging problem, exploring the issue of sustained CNS inflammation as a critical pathogenic mechanism for neurological damage. Despite the tremendous efforts to understand the mechanisms underlying the persistence of HAND, no definitive adjunctive therapeutics have yet entered clinical practice. There is also an unfilled need to develop surrogate markers and more robust and simpler screening instruments for HAND, to allow for earlier detection, for tracking of the course of HAND, and improving the efficiency of clinical trials. Collaborations at Johns Hopkins had been limited by the lack of a central organizing structure for this type of research, and resources to facilitate cross disciplinary and translational research. The JHU NIMH Center has addressed these needs over the past 5 years and has provided a resource to catalyze interdisciplinary research in HIV neuroscience, with the aim of leading to new therapies. The goals of the renewal application of the JHU NIMH Center are to: 1. To facilitate collaborative research in HIV-related neuroscience with the goal of developing a definitive therapy for HIV associated cognitive disorders based on targeting sustained CNS inflammation. 2. To increase resources for HIV-related neuroscience research at JHU and to enhance the productivity of HiV-related neuroscience research locally, nationally and internationally. 3. To encourage high-risk, innovative developmental research in Neuro-AIDS, especially of a cross-disciplinary nature with the specific aim of encouraging investigators (junior or senior) into this field. 4. To use focused medium throughput screening, using in vitro models to identify novel compounds useful for treatment of HIV-associated cognitive dysfunction with the over-arching theme of reducing the sustained CNS inflammation that we believe underlies the development of HAND. 5. To identify and validate surrogate biomarkers based on proteomics and lipomics.

Public Health Relevance

HIV/AIDS is a major threat to global health and urban America, and HIV-associated-neurocognitive dysfunction remains prevalent even in H/V RT-treated people. Our research suggests that one of the drivers for this is sustained inflammation within the brain. Our Center has helped to coordinate and catalyze scientific and clinical resources at JHU to generate novel approaches to therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Center Core Grants (P30)
Project #
5P30MH075673-07
Application #
8291213
Study Section
Special Emphasis Panel (ZMH1-ERB-F (05))
Program Officer
Joseph, Jeymohan
Project Start
2005-07-01
Project End
2016-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
7
Fiscal Year
2012
Total Cost
$1,713,678
Indirect Cost
$568,360
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sacktor, Ned; Nakasujja, Noeline; Redd, Andrew D et al. (2014) HIV subtype is not associated with dementia among individuals with moderate and advanced immunosuppression in Kampala, Uganda. Metab Brain Dis 29:261-8
Meulendyke, Kelly A; Croteau, Joshua D; Zink, M Christine (2014) HIV life cycle, innate immunity and autophagy in the central nervous system. Curr Opin HIV AIDS 9:565-71
Sacktor, Ned; Miyahara, Sachiko; Evans, Scott et al. (2014) Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment. J Neurovirol 20:620-6
Gamaldo, Charlene E; Gamaldo, Alyssa; McArthur, Justin C et al. (2014) Reply: To PMID 23722610. J Acquir Immune Defic Syndr 65:e124-5
Hulgan, Todd; Levinson, Rebecca T; Gerschenson, Mariana et al. (2014) Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy. AIDS 28:1625-33
Yu, Ian W; Espinoza, Diego A; McAlexander, Melissa A et al. (2014) OpenArray profiling reveals no differential modulation of miRNA by positive and negative CD4+ T cell immunoselection. Exp Hematol 42:11-3
Figuera-Losada, Mariana; Rojas, Camilo; Slusher, Barbara S (2014) Inhibition of microglia activation as a phenotypic assay in early drug discovery. J Biomol Screen 19:17-31
Bora, Adriana; Ubaida Mohien, Ceereena; Chaerkady, Raghothama et al. (2014) Identification of putative biomarkers for HIV-associated neurocognitive impairment in the CSF of HIV-infected patients under cART therapy determined by mass spectrometry. J Neurovirol 20:457-65
Bae, Mihyun; Patel, Neha; Xu, Haoxing et al. (2014) Activation of TRPML1 clears intraneuronal A? in preclinical models of HIV infection. J Neurosci 34:11485-503
Meulendyke, Kelly A; Queen, Suzanne E; Engle, Elizabeth L et al. (2014) Combination fluconazole/paroxetine treatment is neuroprotective despite ongoing neuroinflammation and viral replication in an SIV model of HIV neurological disease. J Neurovirol 20:591-602

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