Glutamine Antagonists for the Treatment of Cognitive Deficits, including NeuroAIDs

Some glutamine antagonists have been shown to have anti-cancer activities in multiple preclinical and clinical studies. However the toxicity of the glutamine antagonists at doses necessary for their anticancer effects have hampered their clinical development. Herein we describe a completely novel use for the glutamine antagonists. Using a prototype glutamine antagonist, we show for the first time, at doses significantly less that that used for its anticancer efficacy, that it can selectively abrogate cognitive deficits in the EcoHIV model of neuroAIDs. We show supporting PK and biomarker data. These data predict the use of glutamine antagonists (or their prodrugs or analogs) for the treatment of cognitive deficits in general, and specifically for NeuroAIDs.

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