Ph.D students Alison L. Hill and Daniel I.S. Rosenbloom ’05 received a $100,000 “Phase I” grant for global health research from Grand Challenges Exploration, a program launched by the Bill & Melinda Gates Foundation to fund solutions to health issues in the developing world.
Hill and Rosenbloom, under the direction of Professor Martin Nowak in the University’s Program for Evolutionary Dynamics and in conjunction with other graduate students at Johns Hopkins Medical School, are working to develop a mechanism that can destroy dormant cells infected with Human immunodeficiency virus. This advancement would resolve the primary constraint of currently available anti-viral therapies: they can only attack viruses when they are replicating and cannot target “latent” or hidden viruses that are dormant in infected cells.
“The trouble is that latently infected cells look essentially like healthy cells, and no known mechanism is able to target and destroy them,” Rosenbloom said.
If a patient stops therapy, even temporarily, the virus can survive in these latent reservoirs and begin to replicate again, forcing patients to continue expensive drug therapy for the rest of their lives.
“Patients in developing nations may not even have access to this therapy,” Rosenbloom added. “A cure would eliminate the need for the current expensive treatment model.”
Hill and Rosenbloom have proposed gene therapy as a possible mechanism to deliver a “wake-up call” to latently infected cells, using an HIV-manufactured protein called Tat to trigger the cell out of dormancy and begin replication. This allows for current HIV drugs to target and hopefully eradicate the virus.
According to Hill, the nature of the treatment will pose unique challenges in its administration because it is reliant upon gene therapy, which has not previously been used as a form of therapy. Hill and Rosenbloom said that they hope that they will be able to demonstrate that their gene therapy vector can target and destroy latently infected cells in vitro by next year in order to support the possibility that there is a cure for the disease.
“Our goal is to eradicate all of the latently infected cells, not just 99 percent of them,” Rosenbloom said. Otherwise, he said, “Our approach will not be a complete cure, though it will nonetheless be an important step to achieving one.”
No matter the difficulty, he said it was a necessary undertaking.
“Even if a cure may not be a feasible goal at this point, our generation has a responsibility to more than 30 million living with HIV and nearly 2 million dying each year to at least try our best.”
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