Milan G. Chheda, MD, Associate Professor, Division of Oncology, received the Dr. Ralph & Marian Falk Medical Research Trust – Catalyst Award, to fund his project titled: Genetic arming of Zika virus to treat patients with glioblastoma. The Trust is managed by Health Resources in Action (HRiA), a nonprofit consultancy, which makes funding decisions on behalf of the Trust.
The Catalyst Award program provides support for high-risk, high reward research projects that address significant therapeutic challenges. HRiA carefully selects projects with the potential to create novel pathways for innovative approaches in disease treatment and ultimately lead to cures. Through the program’s seed funding, translational research is effectively facilitated, enabling its implementation into clinical practice in the near term and eventual transition into commercial development.
“With this much-needed research funding, we will be able to complete the most critical stage in our research – determining the best candidate Zika virus strain to first go into patients. The Falk Medical Research Trust has afforded us the opportunity to catapult these ideas into a potentially important treatment that impacts people’s lives.”
Genetic arming of Zika virus to treat patients with glioblastoma
Glioblastoma (GBM) is an extremely aggressive brain tumor, and most patients die within two years. One of the main reasons is that GBM stem cells, a subset of the tumor, are resistant to treatment and can easily cause the tumor to grow again. Additionally, the immune system does not effectively recognize and attack the tumor. However, several years ago, Dr. Chheda, Dr. Michael Diamond, and colleagues developed a new approach to tackle these challenges.
The team’s idea was conceived out of research on the Zika virus (ZIKV), which attacks fetal stem cells in pregnant women. Since GBM stem cells have similarities with these normal fetal cells, the research team wondered whether they could use the natural homing abilities of Zika virus to target and kill the insidious GBM stem cells. They found that the Zika virus can indeed kill these cells from GBM patients, while not affecting normal brain cells.
In experiments with mice that had brain tumors, treatment with the Zika virus extended the average survival time by more than double and even cured many of the mice. Additionally, the Zika virus treatment triggered the immune system to attack the rest of the tumor. The team then engineered a strain of the virus that appears safe in non-human primates.
In the Falk Trust-funded work, Dr. Chheda and colleagues Drs. Michael Diamond and Xuping Xie (University of Texas Medical Branch) will further genetically engineer the virus to make it even safer and more effective. The improved version will engage and activate a robust immune response against the tumor. The most effective version developed through this research will be tested in a first-in-human clinical trial to treat GBM using the Zika virus.