Shunning the Shunt

Published in Hopkins Medicine - Winter 2023

Hydrocephalus, often referred to as “water on the brain,” is a life-threatening buildup of cerebrospinal fluid that affects one in every 770 babies and is the leading cause for brain surgery in children.

The current treatment involves surgically implanting a shunt to drain fluid from the brain. “These shunts save lives,” says pediatric neurosurgeon Dody Robinson, who has performed the surgery many times. “But shunts also tend to malfunction, and when they do, it’s a serious issue. If it happens at 2 a.m., we come in at 2 a.m. to do that surgery.”

The anxiety for young patients and their families is enormous, she says. Children can’t go away to college, or even on a family vacation, without knowing there is a hospital with a neurosurgeon nearby.

Now, Robinson and neuroscientist Lauren Jantzie believe they are less than two years away from launching clinical trials of the first pharmacological treatment for hydrocephalus in babies. “It would be a real game changer,” says Robinson.

There are many conditions that can lead to hydrocephalus, from birth defects to infections to head injuries, or the brain bleeds for which the tiniest, most premature babies are at highest risk. The dream is that a combination of pharmaceuticals that have been proven over the last decade or so to protect and repair brain cells could help a patient’s brain heal itself over time — potentially making a shunt and the associated surgery unnecessary. 

She and Jantzie have had promising results in the lab working to prevent hydrocephalus in infants by combining EPO (erythropoietin), an anti-anemia drug delivered by injection, and melatonin, an over-the-counter supplement many people use to restore their sleep/wake cycle. With funding from the National Institutes of Health, the two expect soon to begin clinical trials to test this approach.

And with a project funded by the Rudi Schulte Research Institute, they are focusing on treating existing hydrocephalus with a combination of melatonin and roxadustat, another anti-anemia drug that has the advantage of being administered orally. They hypothesize that this particular combination can help repair malfunctioning brain and immune cells implicated in the disease process — including cells responsible for maintaining the balance of cerebrospinal fluid in the brain — and even treat other issues associated with the injured brain, including pain, abnormal gait and cognitive deficits.  

“Used individually, these drugs can be effective, but as with chemotherapy for cancer, combining them can increase their effectiveness, and we’re looking for something that is effective 100% of the time,” Robinson says.  

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Illustration by Stuart Briers

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