Currently, over 22 million people have died from AIDS and there are over 42 million people living with HIV/AIDS worldwide. There is no vaccine against HIV, and AIDS, if untreated, will lead to the death of over 95% of infected individuals 10 years post-infection. HIV infects several cell types during the course of infection and progression to acquired immune deficiency syndrome (AIDS). The persistence of latent HIV-infected cellular reservoirs represents the major hurdle to virus eradication with highly active anti-retroviral therapy (HAART), by far the state of the art for treating HIV/AIDS, since latently infected cells remain a permanent source of viral reactivation. HAART remains problematic because of long-term toxicity, development of drug resistance and the inability to target persistent reservoirs.
Our scientists have discovered that Bryostatin 1, a potent PKC modulator, reactivates HIV-1 latency at concentrations that do not activate signal transduction pathways that may result in negative side effects. We have also discovered that Bryostatin 1 synergizes with Histone Deacetylase (HDAC) inhibitors such as valproic acid to antagonize HIV-1 latency. HDAC inhibitors alone do not significantly reactivate HIV-1 latency but reduces 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 [US Patent Pending].
Dr. Eduardo Muñoz, lead inventor and Chief Scientific Officer of VivaCell Biotechnology España states that: "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. 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. This combination therapy will be used in patients being treated with antiretroviral therapy such as HIV-1 protease inhibitors, reverse transcriptase inhibitors, integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors."
VivaCell Biotechnology España, a spinoff from the University of Cordoba, Spain, is an emerging biotechnology company that investigates and develops new medical products derived from medicinal plants and marine organisms, and is currently focused on the preclinical phase of drug discovery.
Aphios Corporation is a biotechnology company that is developing enabling technology platforms and enhanced therapeutic products from medicinal plants and marine organisms for health maintenance, disease prevention and the treatment of certain cancers, infectious diseases and CNS disorders.