Santangelo part of $5.5 million NIH research grant aimed at curing HIV.

This could be the one, the project that Philip Santangelo will be talking about when he’s 80 and retired and rocking on the front porch, in some distant future – a promising future for mankind because, well, this could be the one.

Santangelo, associate professor in the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology, is helping lead a research team that was recently awarded a $5.5 million grant from the NIH/NIAID (National Institute of Allergy and Infectious Diseases) for their role in a national, multi-pronged effort to once and for all cure HIV/AIDS.

“This is like the Holy Grail for a molecular imaging person who’s interested in infectious disease. From my point of view, this is it, this is huge,” says Santangelo, who is partnering with Emory’s Francois Villinger as principal investigators on the research, supported by the aforementioned R01 (which is the original and historically oldest grant mechanism used by the National Institutes of Health, or NIH).

The prospect of eliminating HIV from infected patients may be achievable with novel anti-retroviral therapies, but it would require new tools with greater sensitivity than what is now available. So the research aims to create and improve imaging technology, to better monitor HIV reservoirs.

“This was an RFA [Request for Application]. It was a response to an RFA regarding delivering therapeutics to active viral reservoirs,” Santangelo explains. “At NIH right now, especially at NIAID, they have a huge emphasis on trying to cure HIV.”

But here’s the dilemma Santangelo, et al, are looking at: A person who’s infected with the HIV virus is treated with anti-retroviral therapies. It appears to work. Within a month, the virus is undetectable in the blood stream. It’s been suppressed. But if you take the patient off the therapy, the virus comes back. It rebounds. “The drugs work but they are not sufficient to clear the virus. And really, we don’t know why that is yet,” Santangelo says. “Where is the virus? Where are the active reservoirs during suppression?”

The prospect of eliminating HIV from infected patients may be close at hand, but such a lofty goal will require new tools with greater sensitivity than currently available to monitor the progress of novel anti-retroviral therapies – not only in blood but also in organs that harbor such reservoirs and sites of residual viral replication in vivo.

“We’re not necessarily in this project, quote, 'creating the cure.' But we’re creating a tool that’s going to give us a lot more information about how you might go about doing that,” Santangelo says. “Otherwise, it’s a shot in the dark, you’re just trying different approaches. It’s trial and error. In the drug development world, trial and error is useful, but not ideal, and certainly not efficient.”

This research and resulting improvements in imaging technology, he says, will eventually give drug developers more information than they’ve had before, about how drugs are affecting very specific parts of the body.

“It’s about giving them much more powerful information about what’s happening, as opposed to downstream information,” says Santangelo, whose research areas include molecular imaging, nano-biophotonics, and optical microscopy. The long-term aim is to cure HIV, he adds, “and we’re working on a tool to help facilitate that.”

And that, he adds, is the reason the research got its funding – the NIH wants this tool in its toolbox. The grant covers five years, but it’s been a seven-year journey to this point. It began with a discussion between Santangelo and Emory professor Eric Hunter, whose research is focused on the molecular biology of HIV and other retroviruses.

“We were sitting around a table and Eric basically said, ‘one thing we’d like to know is, where is the virus? Is there a way to image this?’ I said, ‘I have no idea, but let’s see if we can figure that out.’ So I went back to the drawing board and thought about ways to approach the problem,” Santangelo says. “But that’s how it started – a group of people sitting around the table, asking, ‘how do we address this?’ and me being crazy enough to say, ‘I’ll try this,’ because I don’t say no to anything.”

Hunter introduced Santangelo to researcher/pathologist Villinger. They went after and received a $30,000 boost from the Woodruff Foundation, then got $100,000 from the Georgia Research Alliance, “and these were so important in pushing the momentum forward,” Santangelo says.

Then they received $450,000 from the NIH in the form of an Exploratory/Developmental Research Grant Award (R21) and now, $5.5 million, to support the work of an all-star team of researchers, including (among others) principal investigators Santangelo and Villinger, as well as Ray Schinazi, who directs the Laboratory of Biochemical Pharmacology at Emory, and is a co-investigator.

The overall goal, according to Santangelo, is to create or improve an imaging tool that will determine how the virus is being affected by a new drug strategy, and also to help promote new drugs that Schinazi is working on – “to clear HIV, and also to make current drugs more effective,” says Santangelo, who believes that by enhancing current imaging technology, particularly CT (computed tomography, or CAT scanning) and PET (positron emission tomography), he can track the reservoirs, including active viral reservoirs.

“If you can figure out where the reservoirs are, if you can figure out how long they are being affected by the drugs, and how the drugs are actually changing the reservoirs, we might be able to clear them,” says Santangelo, whose eyes light up at the prospect, giving him the look of a kid contemplating a super toy that hasn’t been invented yet. “And if you can clear these reservoirs, you could cure AIDS, and if you can cure AIDS, well, that would be pretty awesome.”