The National Institutes of Health placed a big bet on Oregon scientist Jonah Sacha this week, awarding Sacha and his colleagues an $8.4 million, five-year grant for their work developing a cure for HIV.
Sacha’s current work on a cure for HIV builds on a study his research group published in 2023. The team infected macaque monkeys with the parent virus of HIV and was able to cure them, using stem cell transplantation. The macaques are still alive today and free of the virus.
Jonah Sacha, Ph.D, at OHSU's Oregon National Primate Research Center and Vaccine & Gene Therapy Institute (shown here) has won a grant to work with three patients who were cured of HIV after they received a cancer treatment to try to develop a cure that can be scaled up safely to others.
Kristyna Wentz-Graff / OHSU/Kristyna Wentz-Graff
What makes Sacha’s next research project extraordinary is his collaborators: OHSU announced this week that Adam Castillejo, Paul Edmonds and Marc Franke will contribute to Sacha’s attempt to engineer a cure for HIV.
The men are giving their very cells to the cause.
Castillejo, Edmonds, and Franke are patients who were cured of HIV after they received allogeneic stem cell transplants for cancer.
Sacha says he brought the three men, better known as the “London Patient,” the “Dusseldorf Patient,” and the “City of Hope” patient together in person in Hawaii earlier this year to pitch them on the idea of participating in research. They hope to better understand how they were cured, and to improve the lives of others.
“This is an opportunity for these very unique individuals to share their story, and to participate in this in the hopes of sharing a cure,” Sacha said.
In a further show of support, the NIH selected the grant proposal for a MERIT award, which allows the researchers to extend the grant for an additional five years if they’re making progress.
Sacha is chief of the division of Pathobiology and Immunology at the Oregon National Primate Research Center at OHSU. Lishomwa Ndhlovu of Weill Cornell will co-lead the project.
NIH cuts have placed the future of many research projects in question, and funding for the primate research center is under heightened scrutiny from Oregon’s governor and legislature.
“Receiving a MERIT award in this current climate around science is just incredible. I can’t find words for it honestly,” Sacha said.
Tim Lahey, a physician who studies HIV at the University of Vermont and isn’t affiliated with the research effort, says the award is an incredibly rare honor and a validation of a scientists’ career.
Other scientists have explored stem cell transplants as a possible HIV cure, but none have yet found a way to make it effective and safe.
“We have to hope that they’re the ones that find the holy grail,” Lahey said.
Could stem cell transplants be a path to a cure?
Researcher Jason Reed prepares blood samples from two Mauritian cynomolgus macaques that were cured of simian immunodeficiency virus, part of the Sacha lab's effort to cure HIV.
Amelia Templeton / OPB
Stem cell transplants are risky procedures that kill off a patient’s immune cells and replace them with stem cells from a healthy donor, in effect giving them a stranger’s immune system. The transplants can cure some cancers, but kill some patients in the process and leave others with chronic graft-versus-host disease, a painful chronic condition.
Researchers have known for more than a decade that the procedure will sometimes wipe out the HIV virus too.
It’s a remarkable finding, Sacha says, because HIV is famously impossible to fully clear otherwise. Decades of research hunting for a vaccine and a cure have yet to produce results.
Daily antiretroviral therapy controls the virus and prevents it from transmitting, allowing patients to live full lives with HIV. But because the retrovirus integrates itself into the DNA of its human host, the drugs aren’t a cure.
“As soon as you take that pressure off, the virus will bounce right back and start replicating,” Sacha said. “That’s what makes these cases of HIV cure so remarkable.”
A total of 10 people have been cured to date, according to Sacha. All of them were patients who received stem cell transplants for cancer, and eight of the ten were given cells from donors with a genetic mutation that confers resistance to HIV.
Castillejo, Edmonds, and Franke are three of those cases, at present the only living patients who have come forward publicly.
The research team plans to take biological samples from each patient and perform experiments to better understand and describe the immune responses that led to their cures.
Their goal is to use that knowledge to design a new cure that’s safer than a stem cell transplant. Sacha isn’t willing to share all the details yet of the treatment he has in mind, but says it’s something roughly analogous to new CAR-T cell therapy that trains human immune cells to find and destroy cancer.
The team plans to first test the safety and efficacy of their experimental therapies in mice and non-human primates and aims to launch a human clinical trial in five years. Any credit or profit from a discovery, Sacha says, is something the three participating patients should have rights to alongside the researchers.
“We couldn’t do this without them,” he said.
A key question scientists have about the patients cured of HIV so far has been what exactly was it about the stem cell transplant process that cleared the virus?
Most of the patients received donor cells that came from people who have natural resistance to HIV infection, thanks to a deletion in their CCR5 gene.
However, that so-called “magic gene” might not be enough on its own to cure someone who’s already been infected with HIV. Sacha’s previous research with macaques found that a second process was clearing reservoirs of SIV in the monkeys he cured. That process, known as allogenic immunity, is when immune cells attack cells from a foreign donor.
In stem cell transplants, this allogenic immunity is likely a big part of what wipes out cancer cells. But the same effect also drives graft-versus-host disease, which causes miserable and sometimes deadly complications.
If both allogenic immunity and the CCR5 gene need to work together to clear the virus, it will be harder to engineer a cure that can be scaled up, according to Lahey.
“What is a safer version of that is a tough question,” he said. “I’m really curious to see what comes next.”
There are more than 40 million people living with the virus today, the most at any point in human history. Without a vaccine or a cure, Sacha says, new infections have outpaced the effort to knock back the epidemic with antiretrovirals alone.
“I think within our lifetimes for sure, we will see a cure.”
