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 14 July 2010 Volume 2010:2 Pages 33—37


Review by Single-blind

Peer reviewer comments 3

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

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF] 


Readers of this article also read:

Perioperative management of hemophilia patients receiving total hip and knee arthroplasty: a complication report of two cases

Tateiwa T, Takahashi Y, Ishida T, Kubo K, Masaoka T, Shishido T, Sano K, Yamamoto K

Therapeutics and Clinical Risk Management 2015, 11:1383-1389

Published Date: 15 September 2015

Hematuria following Botox treatment for upper limb spasticity: a case report

Lo TC, Yeung ST, Lee S, Chang EY

Journal of Pain Research 2015, 8:619-622

Published Date: 14 September 2015

A new recombinant factor VIII: from genetics to clinical use

Kannicht C, Kohla G, Tiemeyer M, Walter O, Sandberg H

Drug Design, Development and Therapy 2015, 9:3817-3819

Published Date: 23 July 2015

Acquired hemophilia A: emerging treatment options

Janbain M, Leissinger CA, Kruse-Jarres R

Journal of Blood Medicine 2015, 6:143-150

Published Date: 8 May 2015

A new recombinant factor VIII: from genetics to clinical use

Santagostino E

Drug Design, Development and Therapy 2014, 8:2507-2515

Published Date: 12 December 2014

Patient preference and ease of use for different coagulation factor VIII reconstitution device scenarios: a cross-sectional survey in five European countries

Cimino E, Linari S, Malerba M, Halimeh S, Biondo F, Westfeld M

Patient Preference and Adherence 2014, 8:1713-1720

Published Date: 12 December 2014

Second case report of successful electroconvulsive therapy for a patient with schizophrenia and severe hemophilia A

Saito N, Shioda K, Nisijima K, Kobayashi T, Kato S

Neuropsychiatric Disease and Treatment 2014, 10:865-867

Published Date: 16 May 2014

Evidence supporting the use of recombinant activated factor VII in congenital bleeding disorders

Pär I Johansson, Sisse R Ostrowski

Drug Design, Development and Therapy 2010, 4:107-116

Published Date: 29 June 2010

Does plasmin have anticoagulant activity?

Jane Hoover-Plow

Vascular Health and Risk Management 2010, 6:199-205

Published Date: 26 March 2010