Johns Hopkins Drug Discovery - Project - Chemotherapy-Induced Neropathy
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HIV-Associated Neurocognitive Disorders (HAND)

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As the Therapeutic Core of the Johns Hopkins NIMH Center for Novel Therapeutics for HIV-Associated Neurocognitive Disorders (HAND), JHDD scientists are contributing to the discovery of potential new treatments for HAND.1,2 Administration of intranasal insulin represents one of these approaches, based on several preclinical and clinical reports indicating a role for this hormone in cognitive function3 and HAND pathology.4 Intranasal administration can provide rapid delivery of insulin selectively to the brain via bulk flow along olfactory and trigeminal perivascular channels, and via olfactory bulb axonal transport while maintaining peripheral euglycemia. Studies are now ongoing to test the effect of intranasal insulin on cognition in a rodent model of HAND, and to fully characterize the pharmacokinetics of insulin administered via this route. Efforts to delineate the mechanism of insulin efficacy in HAND are also underway with particular attention being paid to the effect of insulin on energy metabolism in key brain regions, as well as a potential effect on viral load. These experiments will inform study design and dose selection for a clinical trial of intranasal insulin administration in HAND patients currently being enrolled by Johns Hopkins collaborators.

References

  1. Saylor, D.; Dickens, A. M.; Sacktor, N.; Haughey, N.; Slusher, B.; Pletnikov, M.; Mankowski, J. L.; Brown, A.; Volsky, D. J.; McArthur, J. C. HIV-associated neurocognitive disorder – pathogenesis and prospects for treatment. Nat. Rev. Neurol. 2016, 12, 309.

  2. McArthur, J. C.; Steiner, J.; Sacktor, N.; Nath, A. Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap. Ann. Neurol. 2010, 67, 699-714.

  3. Craft, S.; Asthana, S.; Newcomer, J. W.; Wilkinson, C. W.; Matos, I. T.; Baker, L. D.; Cherrier, M.; Lofgreen, C.; Latendresse, S.; Petrova, A.; Plymate, S.; Raskind, M.; Grimwood, K.; Veith, R. C. Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose. Arch. Gen. Psychiatry 1999, 56, 1135-40.

  4. Mamik, M. K.; Asahchop, E. L.; Chan, W. F.; Zhu, Y.; Branton, W. G.; McKenzie, B. A.; Cohen, E. A.; Power, C. Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration. J. Neurosci. 2016, 36, 10683-10695.

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