February 8, 2010

Targeting Hidden HIV: Research Group Licenses New Prostratin Technology

Los Angeles-based AIDS Research Alliance (ARA) has been granted exclusive rights to novel technology that will allow researchers to synthesize prostratin, a natural compound believed to target HIV hiding in inactive CD4 cells in the body, according to a February 8 press release. The technology, developed by researchers at Stanford University, will allow ARA to further develop prostratin without having to collect it from natural resources-an expensive and cumbersome process. 

Prostratin was initially isolated by the National Cancer Institute (NCI) in 1992 as the active constituent of extracts of the tropical plant Homalanthus nutans—whose common names include native poplar and bleeding heart. Naturally found in the Samoan rainforest, the bark of the plant is used in Western Samoa to treat viral diseases such as hepatitis.

In 2001, ARA applied to the NCI for the exclusive license to develop prostratin as an HIV drug. Initial studies conducted by the NCI and ARA indicated that prostratin activates latent HIV in cells, forcing them to produce new virus. This is good news because latent "reservoirs" of HIV hidden throughout the body—including the brain, lymphoid tissue and genital tract—escape the reach of current HIV drugs and the immune system and, thus, remain a major stumbling block to the eradication of HIV. The hope is that if the latent HIV can be activated, then it can be destroyed.

Research has been hampered because prostratin is difficult to obtain, particularly in the quantities needed for practical lab work. The yield of prostratin from H. nutans is low and highly variable; the plant supply is limited; and it's difficult to isolate the compound. What's more, harvesting wild plants, especially in Samoa, also could cause ecological damage. 

The ability to manufacture synthetic prostratin, using a technique developed by Stanford chemist Paul Wender, PhD, and his colleagues, and detailed in a May 2008 issue of Science, has helped researchers overcome these obstacles. 

The method developed my Wender's group uses a renewable resource, croton oil, made from the seeds of Croton tiglium, a small tree cultivated in Asia. Wender's team derived phorbol from the croton oil and then converted it into the structure of prostratin. 

"Wender's genius removes a major hurdle to the therapeutic development of this promising compound," said Carolyn H. Carlburg, president of ARA. The ability to produce prostratin synthetically will significantly reduce future costs, making prostratin a more viable drug candidate, she said.

"When used in combination with existing antiretroviral drugs, prostratin may one day help treating physicians eradicate all virus from the body—a feat not yet possible using existing therapies," stated Stephen J. Brown, MD, medical director at ARA.

Search: Prostratin, AIDS Research Alliance, Stanford, Wender, reservoirs, latent HIV, Homalanthus nutans, Croton tiglium, croton oil, Samoa, native poplar, bleeding heart

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