? THERAPEUTIC CORE The Therapeutic Core of the Johns Hopkins NIMH Center for Novel Therapeutics of HIV-associated Cognitive Disorders (HAND) will play an integral role in the development of new therapeutic agents for HAND. The Therapeutic Core is operated by the Johns Hopkins Drug Discovery (JHDD) program, an integrated drug discovery team with extensive Pharma experience and capabilities in medicinal chemistry, assay development/screening, drug metabolism, pharmacokinetics, and animal pharmacology. Recent metabolomics studies profiling the cerebrospinal fluid (CSF) from cART-treated HIV patients showed increases in glutamate in patients with HAND compared to those without the symptoms. Other CSF biomarker studies showed an association between accumulation of sphingomyelin and ceramide and deficits in speed of information processing and working memory. These findings collectively provide the rationale for exploring glutamate homeostasis (Objective 1) and lipid metabolism (Objective 2) as mechanistic platforms to develop new HAND therapies with clinical relevance to CART treated HIV patients. In addition, our core will play a central role in providing HAND researchers with laboratory and consultancy services in drug discovery and development as well as engaging internal/external academic investigators and Pharma to evaluate new therapies being developed for other indications in HAND preclinical models (Objective 3). Working closely with the centers? Biomarker and Clinical cores, these activities should facilitate translational research towards developing novel therapeutics for HAND relevant to cART-treated patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Center Core Grants (P30)
Project #
5P30MH075673-13
Application #
9690177
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2019-07-09
Budget End
2020-02-29
Support Year
13
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Sacktor, Ned (2018) Changing clinical phenotypes of HIV-associated neurocognitive disorders. J Neurovirol 24:141-145
Capó-Vélez, Coral M; Morales-Vargas, Bryan; García-González, Aurian et al. (2018) The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders. Sci Rep 8:1829
Rubin, Leah H; Sacktor, Ned; Creighton, Jason et al. (2018) Microglial activation is inversely associated with cognition in individuals living with HIV on effective antiretroviral therapy. AIDS 32:1661-1667
Chaudhuri, Amrita Datta; Dastgheyb, Raha M; Yoo, Seung-Wan et al. (2018) TNF? and IL-1? modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis 9:363
Rojas, Camilo; Stathis, Marigo; Coughlin, Jennifer M et al. (2018) The Low-Affinity Binding of Second Generation Radiotracers Targeting TSPO is Associated with a Unique Allosteric Binding Site. J Neuroimmune Pharmacol 13:1-5
Chan, Parco; Saleem, Mahwesh; Herrmann, Nathan et al. (2018) Ceramide Accumulation Is Associated with Declining Verbal Memory in Coronary Artery Disease Patients: An Observational Study. J Alzheimers Dis 64:1235-1246
Mohamed, M; Barker, P B; Skolasky, R L et al. (2018) 7T Brain MRS in HIV Infection: Correlation with Cognitive Impairment and Performance on Neuropsychological Tests. AJNR Am J Neuroradiol 39:704-712
Sacktor, Ned; Skolasky, Richard L; Moxley, Richard et al. (2018) Paroxetine and fluconazole therapy for HIV-associated neurocognitive impairment: results from a double-blind, placebo-controlled trial. J Neurovirol 24:16-27
Barinka, Cyril; Novakova, Zora; Hin, Niyada et al. (2018) Structural and computational basis for potent inhibition of glutamate carboxypeptidase II by carbamate-based inhibitors. Bioorg Med Chem :
Lemberg, Kathryn M; Vornov, James J; Rais, Rana et al. (2018) We're Not ""DON"" Yet: Optimal Dosing and Prodrug Delivery of 6-Diazo-5-oxo-L-norleucine. Mol Cancer Ther 17:1824-1832

Showing the most recent 10 out of 164 publications