On the cusp of a cure?

by Jason Parsley
Thursday Jul 14, 2011

A tree in Samoa may be the crucial link to a cure for HIV, but money is needed to move research and development along

For years the AIDS Research Alliance in California has been at the forefront of researching a cure for HIV. And now they think they may have found it - prostratin.

The compound was first discovered in the Pacific island nation of Samoa by native healers in the 1800s. They would make tea with it and use it to treat viral hepatitis.

Technically the compound is a non-tumor-promoting phorbol ester derived from the Mamala tree (Homalanthus nutans).

"We've got HIV treatment down. Now we need a cure. The stumbling block to a cure are the reservoirs and we think prostratin is part of that answer. As a long-term survivor myself, I'm very excited about this," said Art McDermott, vice president of development for ARA. "We're the only ones with a drug in the pipeline. But we need the public's help to move this research forward. Because of budget cuts we've had to rely more and more on private giving."

It wasn't until 1997 when researchers first discovered that HIV can lay dormant and hide in pockets called reservoirs throughout the body for decades escaping even the most powerful anti-HIV drugs and springing to life as soon as treatment stops. That's one of the major reasons HIV has been so difficult to treat and why those infected must stay on drugs for life.

"As soon as you get off meds the HIV comes roaring back and starts the infection all over again," McDermott said.

Researchers at the National Cancer Institute were the first ones to discover that prostratin could possibly be used as an anti-HIV drug. In the early 90s they began testing their large repository of chemicals gathered from all over the world to see if any of them could be used as anti-HIV drugs. Prostratin popped up as a possible one, however, after some testing they found that, while it did stop HIV from infecting healthy cells, it also increased the virus production in cells that were already infected, but dormant. Because of the increased viral production they put further research and testing on hold.

But it's the increase that researchers would later find to be beneficial. Because prostratin activates the dormant HIV hidden in the reservoirs it also allows the newly activated HIV to be attacked by anti-HIV drugs.

When Dr. Stephen Brown, vice president and medical director of ARA, took the job in 1997 one of the things the board decided upon is that they wanted him to start looking for things useful in attacking those reservoirs.

"No one knew much about the reservoirs at that time and this was way before anyone was thinking about them," he said.

It wasn't until 1999 when Brown first learned of prostratin in a presentation addressing whether or not the compound should be reconsidered in the era of Highly Active Antiretroviral Therapy (HAART).

"I was absolutely thrilled because this was exactly the thing we were looking for," he said.

Research, however, moved slowly because of the difficulty in getting prostratin, since it was only found in the bark of the Mamala Tree. It wouldn't be until 2008 when Dr. Paul Wender of Standford discovered how to synthetically create the compound. ARA now holds the exclusive National Institute of Health license to develop it.

"Every two people that access HIV treatment another five people become infected," McDermott said. "We're never going to be able to treat our way out of the epidemic."

But in order to continue the testing and get clinical trials in humans the organization needs funding. McDermott said unfortunately the federal government is focusing their resources on a vaccine rather than a cure, so there isn't much money to be had there.

If ARA had all of the money they needed Brown said it would take about 1 to 2 years to complete the human trials. Realistically though, he said, they're still about 5 years away from any sort of drug making it to the pharmacy. Besides reaching out to new donors they're also looking to form a partnership with a drug company to speed up the process.

McDermott estimates ARA needs another 2 million to get the clinical trials in humans.

"Eventually we hope that with this medication by itself, or in combination with others, it could get people off of medications completely," Brown said. When asked if that meant a cure for HIV he responded, "yes but a lot of people don't like to use that term. It's still controversial."

Even if prostratin proves not to be a cure Brown believes it may lead to a new class of drugs called HIV reservoir ablative agents that would attack the reservoirs.

"We're hoping to begin a new approach with the flushing of these reservoirs," Brown said.

Viist for more information.

Prostratin Timeline:

1800s - Polynesian healers start using the Mamala tree in native medicines. In Samoa a tea from the tree's bark is used to treat viral hepatitis.

1987 -- Ethnobotanist Dr. Paul Cox meets a native healer in Samoa who introduces him to 121 different indigenous treatments including the tea made with the Mamala bark.

1991 - Cox sends a sample of the tea to the National Cancer Institute, which screens it for it's potential at fighting cancer. NCI isolates an active molecule from the tea and labels it "prostratin."

1992 - NCI screens prostratin to see if it has any anti-HIV abilities. They discover it stops HIV from infecting healthy cells. But it also activates HIV production in cells that are infected but dormant. It's deemed counterproductive and shelved for the next 7 years.

1999 - Dr. Stephen Brown at the Aids Research Alliance learns of prostratin from a presentation.

2002 - ARA and UCLA are awarded a grant from California AIDS Research Center to develop methods to measure the effects of prostratin on HIV reservoirs. Scientists from ARA and UCLA publish the first scientific paper on prostratin in Journal of Virology.

2003 - The world's first symposium is held on HIV reservoirs

2004 - Another paper published about prostratin reports on prostratin's ability to act as an "entry inhibitor," stopping HIV from infecting healthy cells.

2005 - All federally funded prostratin research ends when the Bush administration closes the NIH-DART (National Institute of Health, Development of AIDS Related Therapeutics Program) program.

2005-2007 - ARA has to rely on private funds to recruit a major contract research lab to continue the Federal and Drug Administration's required pre-clinical studies. Over the next 18 months key toxicology studies proves prostratin poses no risk of causing cell mutation or tumors.

2007 - ARA collects blood samples from 6 HIV positive patients to assess the lowest amount of prostratin needed to activate HIV.

2008 - Dr. Paul Wender discovers how to create prostratin synthetically, which in turn reignites the research of prostratin.

Present - Clinical trials in animals are taking place, but money is needed to get the trials into human beings.

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