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

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...

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Bibliographic Details
Published in:Neurobehavioral HIV medicine 2010-07, Vol.2, p.33
Main Author: Everall, Ian
Format: Article
Language:English
Subjects:
Antiretroviral therapy
Apoptosis
Caspase
Caspase-3
CD4 antigen
Cell culture
Clinical trials
Cognition
Glycoprotein gp120
HIV
Human immunodeficiency virus
Morbidity
Motivation
Neurodegeneration
Neuroprotection
Quality of life
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Summary: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.
ISSN:1179-1497
1179-1497
DOI:10.2147/NBHIV.S8711