Back to Browse Journals » Neurobehavioral HIV Medicine » Volume 2

Amelioration of caspase 3,7 activity by SP01 in human primary neurons exposed to HIV

Authors Amol Shah, Gursharan Chana, Ginger R Lucero, et al

Published Date July 2010 Volume 2010:2 Pages 33—37

DOI http://dx.doi.org/10.2147/NBHIV.S8711

Published 14 July 2010

Amol Shah1, Gursharan Chana1,2, Ginger R Lucero1, Eliezer Masliah3, Cristian L Achim1, Laurent Lecanu4, Vassilios Papadopoulos4, Janet Greeson5, Ian P Everall1,2

1Department of Psychiatry, HIV Neurobehavioral Research Center, University of California, San Diego, School of Medicine, La Jolla, CA, 92093, USA; 2Department of Psychiatry, The University of Melbourne, Royal Melbourne Hospital, VIC, 3050, Australia; 3Department of Neurosciences, University of California, San Diego, School of Medicine, La Jolla, CA, 92093, USA; 4The Research Institute of the McGill University Health Centre and Department of Medicine, McGill University, Montreal QC, Canada; 5Samaritan Pharmaceuticals, Las Vegas, Nevada

Abstract: Despite development of antiretroviral therapy (ARV) HIV associated neurocognitive disorder (HAND) continues to be a significant cause of morbidity. As ARVs are not entirely effective against HAND, there is significant motivation to discover novel therapies that are targeted towards the treatment of HAND. A novel formulation of procaine hydrochloride, SP01, is one potential molecule which has shown promise. Phase I clinical trials have found SP01 treatment to significantly increase CD4 cell counts and quality of life parameters in HIV infected patients. To assess SP01’s potential use for HAND we utilized an in vitro human ­primary neuron culture model and conducted co-exposure experiments with gp120 ([BaL] 300 pg/mL) or HIV (BaL) 500 pg/mL) with or without SP01 (10 µM) and measured the activity of the pro-apoptotic caspases 3/7 using a quantitative luminescence assay. Both gp120 and HIV resulted insignificant increase in caspase 3/7 activity from controls (P < 0.05). This effect was ameliorated with co-exposure with SP01 (P < 0.05). The reduction in activity of caspases 3 and 7, which are well known to be cellular triggers for apoptosis, signifies that SP01 is likely to have neuroprotective effects against HIV induced neurodegeneration via inhibition of pro-apoptotic cascades. Given its success in clinical trials and in vitro experiments, SP01 seems to be a legitimate contender in the fight against HAND.

Keywords: HIV, SP01, neurotoxicity, caspase, HAND, neuroprotection

Download Article [PDF] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

Nagelschmitz J, Blunck M, Kraetzschmar J, Ludwig M, Wensing G, Hohlfeld T

Clinical Pharmacology: Advances and Applications 2014, 6:51-59

Published Date: 19 March 2014

Population pharmacokinetics of olprinone in healthy male volunteers

Kunisawa T, Kasai H, Suda M, Yoshimura M, Sugawara A, Izumi Y, Iida T, Kurosawa A, Iwasaki H

Clinical Pharmacology: Advances and Applications 2014, 6:43-50

Published Date: 4 March 2014

Nanostructured polyurethane-poly-lactic- co-glycolic acid scaffolds increase bladder tissue regeneration: an in vivo study

Yao C, Hedrick M, Pareek G, Renzulli J, Haleblian G, Webster TJ

International Journal of Nanomedicine 2013, 8:3285-3296

Published Date: 28 August 2013

Antibiofilm surface functionalization of catheters by magnesium fluoride nanoparticles

Lellouche J, Friedman A, Lahmi R, Gedanken A, Banin E

International Journal of Nanomedicine 2012, 7:1175-1188

Published Date: 1 March 2012

Immune activation and neuropsychiatric symptoms in human immunodeficiency virus type 1 infection

Schroecksnadel S, Kurz K, Weiss G, Fuchs D

Neurobehavioral HIV Medicine 2012, 4:1-13

Published Date: 16 January 2012

Detemir as a once-daily basal insulin in type 2 diabetes

Nelson SE

Clinical Pharmacology: Advances and Applications 2011, 3:27-37

Published Date: 18 August 2011