Prostratin: A Potential Cure Strategy
Prostratin is a naturally occurring, non-tumor promoting phorbol ester found in the bark of the mamala tree. Paul Alan Cox, PhD, an ethnobotanist, originally identified prostratin when he met native healers in Western Samoa, who used a tea made from mamala bark to treat hepatitis. Samples of this tea were sent to scientists at the National Cancer Institute [NCI], one of the institutes of the National Institutes of Health [NIH], where new compounds are screened for their potential use in fighting disease. Dr. Michael Boyd and his colleagues at NCI isolated the active chemical from the mamala tea, prostratin, and discovered its potential effects against HIV.
Prostratin is a member of a distinct subclass of protein kinase C (PKC) activators. Activation of the PKC pathway triggers a cascade of events that result in the transport of important transcription factors that ultimately “turn on” viral gene expression. A variety of studies conducted by AIDS Research Alliance and other scientists have confirmed the specific activity of prostratin and its effects within the cell. Several reports have demonstrated prostratin’s potent antiviral activity against various strains of HIV.
AIDS Research Alliance has confirmed prostratin’s dual effect, reactivating HIV-1 in memory CD4+ T cells that harbor latent proviruses, while down-regulating the CD4 receptor, precluding new HIV infections. Prostratin has also been shown to activate latent virus in primary CD4+ T cells, and peripheral blood mononuclear cells (PBMCs) from patients on HAART with undetectable plasma viremia; resting CD4+ T infected ex vivo tonsil tissues; and ex vivo in thymocytes. These studies highlight the potential of prostratin as a novel therapeutic that specifically targets the latent HIV reservoirs.
Prostratin and AIDS Research Alliance
AIDS Research Alliance has been granted an exclusive license by the National Institutes of Health [NIH] to develop prostratin as an anti-HIV drug targeting the viral reservoirs. AIDS Research Alliance subsequently was awarded a grant under the NIH Development of AIDS Related Therapeutics Program [NIH-DART] to perform pre-clinical studies on prostratin.
In 2009, AIDS Research Alliance filed patent applications in the United States, the European Community, and other developed countries with significant HIV populations (Methods of Administering prostratin and Structural Analogs Thereof, US Application No.: 12/937,364, European Patent Application No. 09730430.7). As a non-profit organization, AIDS Research Alliance seeks to ensure that access to prostratin, particularly for patients in developing countries, will be available after it obtains FDA approval for its use in humans.
Also in 2009, Stanford University granted AIDS Research Alliance exclusive rights to a novel technology to produce prostratin synthetically. This technology will decrease significantly the cost of production, and allow our scientists to screen for potential follow-on analogs with improved potency and pharmacokinetics, and reduced toxicity. The ability to produce prostratin synthetically will make it accessible in the developing world, where the need for a cure is most urgent.
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