Stanford researchers have unveiled groundbreaking findings that could revolutionize HIV treatment, demonstrating that EBC-46 – a compound already making waves in cancer therapy – shows exceptional promise in targeting and eliminating dormant HIV infections.
The research team, led by Paul Wender, the Bergstrom Professor of Chemistry at Stanford's School of Humanities and Sciences, discovered that EBC-46 and its analogs excel at activating dormant HIV-infected cells, achieving unprecedented success rates in laboratory studies. This breakthrough, published January 24 in Science Advances, represents a significant advance in the "kick and kill" strategy for HIV eradication.
Unprecedented Efficacy in Targeting Dormant HIV
In laboratory experiments, synthetic analogs of EBC-46 demonstrated remarkable effectiveness, successfully reversing latency in 90% of treated cells. This achievement represents a four-fold improvement over bryostatin, the current leading latency reversing agent, which only activates approximately 20% of dormant cells.
"We're pleased to report that EBC-46 performed extremely well in preclinical experiments as part of a 'kick and kill' therapeutic," said Wender. "While we still have a lot of work to do before treatments based on EBC-46 might reach the clinic, this study marks unprecedented progress toward the as-yet-unrealized goal of eradicating HIV."
From Australian Rainforest to Laboratory Success
Originally discovered by QBiotics in the Australian blushwood tree (Fontainea picrosperma), EBC-46 – technically known as tigilanol tiglate – works by binding to protein kinase C (PKC), an enzyme crucial to various cellular processes. The compound's limited natural availability was overcome through a synthetic production method developed by Wender's team in 2022, enabling the creation and testing of multiple analogs.
Addressing a Global Health Crisis
The potential impact of this discovery is significant, considering the global HIV burden. According to the Joint United Nations Programme on HIV/AIDS, approximately 40 million people currently live with HIV, with nearly two million new infections annually. While current antiretroviral therapies (ARTs) have transformed HIV from a lethal infection to a manageable condition, they require lifetime adherence and pose significant economic challenges.
"Part of the solution to the global HIV problem is addressing the 40 million people who are HIV positive," Wender explained. "Easing the medication burden and economic losses posed by the current HIV regimen, especially in developing countries, is critical."
Dual-Purpose Promise
The compound's versatility is particularly noteworthy. EBC-46 recently received FDA approval in 2024 for treating soft tissue sarcomas in humans, following successful veterinary applications where it demonstrated an 88% cure rate for mast cell tumors in dogs.
Building on these promising results, the research team has initiated animal model studies of HIV treatment, with the ultimate goal of advancing to human clinical trials. The potential for EBC-46 to serve as both an anticancer agent and an HIV eradication tool represents a remarkable development in medical research.
"The fact that we may be able to make a dramatic difference in people's lives with EBC-46 is what keeps us up late at night and gets us up early in the morning," concluded Wender.
