By Shannon Turgeon
Photography by Joshua Franzos
In fall 2018, Megan Culler Freeman, assistant professor of pediatrics, School of Medicine, was working as a pediatric infectious diseases fellow at UPMC Children’s Hospital of Pittsburgh.
This part of her medical training coincided with a wave of children across the nation who were presenting with sudden paralysis.
Doctors suspected that the paralysis was caused by a respiratory virus known as enterovirus D68 (EV-D68).
When EV-D68 was discovered in the 1960s, it did not cause neurologic disease.
However, two mysteries emerged in 2014 when a high volume of patients with the infection began experiencing paralysis, indicating a change in the virus.
In addition, only some of the children who became infected with EV-D68 were experiencing paralysis.
Freeman met and cared for all the patients with this condition at Children’s Hospital in 2018.
“We don’t have any specific treatments for enteroviruses, so there’s not an antienterovirus drug I can provide. The only thing we really have to offer in the hospital is supportive care, so things like pain control and mechanical ventilation if somebody needs breathing support,” she said.
“We knew very little about the appropriate therapies that might be more specific or help them improve.”
That experience paved the way for the research that she does today.
On Friday, June 12, Freeman will present “Understanding How Viruses Cause Paralysis” as part of the 2026 Senior Vice Chancellor’s Research Seminar Series. (Join the lecture here.)
To get to the root of how EV-D68 evolved to cause paralysis, Freeman and her lab needed to study how the virus replicated in the tissues of the human spinal cord.
Their solution was to develop a human spinal cord organoid model.
“We start with induced pluripotent stem cells and feed them a recipe of growth factors over the course of several weeks. Those growth factors encourage the stem cells to develop into the cells of the spinal cord. There are multiple different cells in the dish—the organoid structure—that are representative of cells that you would find in a human spinal cord,” Freeman said.
Freeman and her lab members discovered that the EV-D68 virus from the 1960s did not infect their organoids, but the variants of the virus from 2014 and 2018 caused significant infection.
Scientists already knew that neurons were infected by the virus, but the spinal cord organoid demonstrated that astrocytes, supportive cells that help neurons, were also affected.
Further research found that T cells, which are part of the body’s immune response, play an important role in enterovirus-induced paralysis.
“If those T cells are blocked, the paralysis phenotype is much improved, even though there’s still virus replicating in the spinal cord,” she explained.
EV-D68 infections subsided in 2020. This was likely due to masking and social distancing measures during the COVID-19 pandemic that disrupted the circulation and changed the ecology of respiratory viruses.
When EV-D68 was seen again in 2022, it was not associated with paralysis in children who were infected.
“We don’t yet understand why it happened, but my lab recently learned that viruses that circulated that year cannot get into the cells of the spinal cord. It might be related to a way that the virus has changed,” she said.
Freeman remains motivated to keep pursuing answers around EV-D68 and other viruses through her interactions with patients.
“When you interact with patients who have a disease where you don't have anything specific to offer them, you can tell them what you’re trying to discover that will help them, or other kids like them, in the future,” she said.
“My lifelong dream would be to understand something about enterovirus biology, and viral biology in the spinal cord and brain, that would allow us to come up with universal treatments. We still have a lot of work to do to be able to do that.”