Bryostatin-1 will be coupled with HDAC inhibitors to reduce the concentration at which HIV-1 is released from latent reservoirs.
Aphios inked an agreement with VivaCell Biotechnology to develop a combination therapy for HIV latency. They will investigate bryostatin-1, a potent PKC modulator, along with HDAC inhibitors.
Bryostatin-1 reactivates HIV-1 latency without activating signal transduction pathways that may result in negative side effects, says Aphios. The company states bryostatin-1 synergizes with HDAC inhibitors, which reduces the concentration at which HIV-1 is released from latent reservoirs. HDAC inhibitors alone do not significantly reactivate HIV-1 latency but reduce the concentration of bryostatin-1 by at least one order of magnitude to about 1 nanomolar at which HIV is released from its latent reservoirs
“From our experiments using a specific and suitable model for HIV-1 reactivation, we determined which combinations of bryostatins and HDACs inhibitors synergize to antagonize HIV-1 latency,” says Eduardo Muñoz, M.D., Ph.D., lead inventor and CSO of VivaCell. “This finding is essential for the formulation of the combination therapy using low nanomolar concentrations of bryostatins.
“We also showed that bryostatin-1 downregulates the expression of the HIV-1 receptors CD4 and CXCR4 and prevents HIV-1-induced cytotoxicity. While HDACs can be administered in continuous dosing protocol, bryostatins can be administered following a cyclical dosing protocol.”