Scientists are experimenting with strands of the Zika virus, hoping to be able to integrate it into the treatment of glioblastoma.
Could the Zika virus be used for health? A new study suggests that it could, despite - or rather, because of - its tendency to target and destroy neural progenitor cells, which are brain stem cells that differentiate into neurons and glial cells in the central nervous system. This is why the babies of mothers infected with Zika during their pregnancy are often born with microcephaly.
However, this might also make the Zika virus a viable "weapon" against glioblastoma stem cells, which are undifferentiated cells that promote the development of glioblastoma, a particularly aggressive form of brain cancer.
The research was co-directed by Drs. Michael Diamond and Milan Chheda, both from Washington University School of Medicine in St. Louis, MO, alongside Dr. Jeremy Rich, from the University of California School of Medicine in San Diego.
"We knew that [the] Zika virus selectively targeted neuroprogenitor or stem cells in the brain in developing fetuses. A postdoctoral fellow, Zhe Zhu [first study author], hypothesized that it might be able to infect and kill glioblastoma cells, especially the ones that are hard to eradicate (cancer stem cells)," Dr. Diamond told Medical News Today.
The preliminary findings of this study were published today in The Journal of Experimental Medicine.
Zika targets cancer stem cells
Glioblastoma stem cells are particularly resistant, even to aggressive forms of therapy, meaning that tumors typically return and survival rates are poor. These cancerous cells can "trump" the body's immune system, so neutralizing them would allow for a more effective removal of the original tumor.
To test their hypothesis that the Zika virus could target and kill glioblastoma stem cells, the team first conducted experiments in vitro, using glioblastoma specimens collected from tumors that had been surgically removed.
The experiments showed that the Zika virus targeted and killed glioblastoma stem cells, rather than any other glioblastoma cells, or other types of brain cells.
"We were surprised at how selective [the] Zika virus was in tumor cell killing. It efficiently infected and killed the cancer stem cells but did not infect well the differentiated tumor cells or the neighboring healthy cells," Dr. Diamond told MNT.
Following this step, the researchers sought to replicate the results in vivo, using laboratory mice that were injected with a modified strain of the Zika virus. In this case, it was found that the virus decelerated tumor growth, improving the animals' life expectancy.
The next step was to create a less virulent strain of the Zika virus, which is more susceptible to the body's natural immune response than the "wild" strain.
It was found that this modified strain still targeted glioblastoma stem cells preferentially. Moreover, its effectiveness was enhanced by temozolomide, which is a chemotherapy drug that normally fails to affect glioblastoma stem cells.
'We need to better understand Zika'
They noticed that, unlike Zika, the West Nile virus indiscriminately targeted and killed glioblastoma stem cells and non-cancerous cells alike.
"[W]hile [the] West Nile virus can also kill cancer stem cells, it also killed healthy neurons. Obviously, this would preclude its use as a tumor therapy," Dr. Diamond told us, explaining that it is Zika's "relative selectivity for stem cells" that sets it apart as a potential tool for treatment.
The scientists involved in the research are hopeful about the encouraging results so far. But as they explained to MNT, there is still a long way to go until they can confirm that Zika can, in fact, be harnessed to treat glioblastoma.
"While we are hopeful about developing this [...] into a treatment for human glioblastoma patients, there are many things we need to confirm and extend, [such as verifying that] the attenuated [less virulent] virus that we generate is stable."
Dr. Michael Diamond
To do this, further in vitro and in vivo experiments are needed. Dr. Diamond told us, "We would like to engineer more mutations in the virus to enhance its safety profile, [and] we [also] need to show the virus can protect against human tumors in mice."
Furthermore, "we need to understand better the relative contribution of the virus and immune system to tumor clearance," he added.
A better understanding of the virus's mechanism is also needed, Dr. Chheda told us, if it is to be modified in a way that makes it safe as well as effective.
"We need to better understand why [the] Zika virus is so specific against the cancer stem cells. We have clues, but better understanding this will help us further engineer the virus to make it even more efficacious and safe," he told MNT.