By GREGORY ZELLER
A cure for AIDS? Let’s not get ahead of ourselves.
Few people understand the molecular world like Stony Brook prof Carol Carter, and the longtime researcher will tell you that such a grandiose achievement may be a decade away or more.
And besides, she’s not working on a cure. But her unique method of targeting cellular factors that release the HIV-1 virus from infected cells – rather than targeting the virus itself – could lead to a viral inhibitor that stops HIV’s path of cellular destruction, giving an immune system the time it needs to do its thing.
The potential antiviral breakthrough is not limited to HIV-1, and Carter isn’t the only researcher on the case. But her inhibitor has already stopped the spread of HIV in tissue samples, and she’s on the brink of creating first-in-class molecules that can do the same in more complex biological organisms – plants first, then small animals.
From there, the potential healthcare impact, and commercialization possibilities, are staggering. The Centers for Disease Control report that at the end of 2012, an estimated 1.2 million people aged 13 and up were living with the HIV infection and the average cost for treatment over the lifetime of each bested $379,000. And those are just U.S. numbers.
AVERT, an international charity that’s tracked the epidemic for 30 years, estimates that almost 37 million people around the world were HIV-positive as of 2014, and the immunodeficiency was killing 1.2 million of them annually.
Carter’s potential market is clear. And with other researchers around the world targeting other viruses, the viral inhibitor could someday be the weapon of choice against dozens of aggressive invaders – including some, like HIV, that currently have the upper hand.
“It’s one of those diseases that’s humbling us,” Carter noted. “We don’t have an effective vaccine, and the infection – though controllable, depending on where you live – is holding its own.”
Its days of dominance, however, may be numbered.
Current treatments for HIV and other viral infections involve pharmaceutical agents that attack the viruses themselves. But this encourages “resistant variants,” Carter noted – the viruses mutate and go on about their destructive business.
Instead, Carter is targeting cellular functions that certain viruses must perform to spread, colloquially known as “budding.”
When a virus infects a cell, it wants to replicate and spread to other cells – to “get out of Dodge,” as Carter put it. Some viruses simply kill the cell, and when it falls apart, the viral proteins float along to the next healthy cell. That’s how polio advanced.
In other cases, virus molecules assemble at the periphery of an infected cell and push, bulging the cell membrane until nascent viral particles burst out – the cellular equivalent of, say, popping a pimple – and move onto their next target. Known as “budding,” this is HIV’s basic travel plan.
Carter’s inhibitor aims to stop the viral budding process without affecting the cell’s ability to perform healthy budding as necessary. The science grows out of a discovery she made 15 years ago involving a protein called TSG101, a key facilitator of a virus’ ability to move from cell to cell.
Back in 2001, Carter and her SBU lab-mates, working with researchers at the University of Utah and Rockefeller University, identified TSG101 – common to plant, yeast and human cells – as the protein viruses interact with as they move around.
Subsequent research by other investigators revealed that, “in many cases, TSG was also necessary for budding and the release of viruses.”
Enter the chemical inhibitor, which blocks a virus’ ability to attract TSG101. Carter and her team have been able to stunt viral progress in tissue cultures, but now comes the hard part: Reducing the amount of chemicals needed to stymie HIV-1 in complex biological organisms.
“We’re not at a dosage yet that’s acceptable if you want to move this into a human system,” Carter noted. “We need to lower the amount of drugs needed to effectively block the virus.”
Many factors will determine how long it takes researchers to get from here to there. The myriad investigators applying the TSG101/budding-blocking science to different viruses are all at similar developmental stages, according to Carter, and the X factor in each project is money.
While she doesn’t yet have a company, Carter’s inhibitor work has already attracted capital: In November, a SUNY program funded by the National Institutes of Health awarded Carter’s team $50,000.
That money, it’s hoped, will lead to federal funding to cover the $300,000 or so needed to cover the next two steps: identifying the best chemical compound to stop HIV budding in plant cells, and then determining the lowest possible dose to achieve the same results in small animals.
That’s a “two-to-three-year venture,” Carter said, at which time the SBU investigators may turn to private funding. Carter has already jumpstarted that process, attending SBU’s Innovation Boot Camp this winter to polish her investor pitch.
The camp was “intense and time-consuming,” the scientist noted, but will prove invaluable when “Vexit” – for “viral exit,” the name her team used during camp sessions – reaches the VC stage.
“We’re trying to attract private capital, but you need to demonstrate efficacy in small animal models, leading up to trials where you test for safety and bio-availability in non-human primates, and then maybe clinical trials.”
That could normally take a decade or more, but the viral inhibitor might be accelerated by need. The World Health Organization estimates that treatment of global HIV infections is already a $13.5 billion annual market, signifying a worldwide demand that could speed Carter’s potential epidemic-smashing inhibitor through the pipeline.
“If you track the route of the HIV drugs on the market now, they didn’t require 15 or 20 years to develop, just because of the need,” Carter said. “I’d imagine that if we reach clinical trial stage 1 or 2 and the FDA sees excellent promise, it might route this the way it’s routed other HIV drugs.”