Helping babies is their shared obsession. Since they first met a decade ago, pediatric neurosurgeon Dody Robinson and neuroscientist Lauren Jantzie have been collaborating on research to better understand the disease processes that cause brain damage in infants and to identify targeted therapies that might prevent and reverse the conditions children develop as a result.

Since 2016, the two have concentrated their joint efforts on finding a better way to both prevent and treat hydrocephalus, a life-threatening buildup of cerebrospinal fluid. Often referred to as “water on the brain,” hydrocephalus affects 1 in every 770 babies, according to the Hydrocephalus Association, and is the leading cause for brain surgery in children. Now, with the support of a new $250,000 grant from the Rudi Schulte Research Institute (which also awarded the duo a grant for their hydrocephalus work in 2020), Robinson and 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, a professor of neurosurgery at Johns Hopkins Children’s Center who also runs her own Johns Hopkins research lab. The current treatment involves surgically implanting a shunt — Rudi Schulte was a watchmaker who invented the first hydrocephalus shunt in 1961 — to drain fluid from the brain. “These shunts save lives,” says Robinson, who has performed the surgery many times. “Before Schulte’s invention, the prognosis for hydrocephalus was pretty grim. 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.

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. “And if patients have to take a couple pills every day for the rest of their lives, it would be a lot better than worrying about their shunt every day,” says Robinson, who in October was named president-elect of the American Academy of Neurological Surgery.

She and Jantzie, who joined Johns Hopkins in 2019, have focused on better understanding the fundamental biological mechanisms underlying brain health, and on how and why specific medications might restore the cells that keep the brain functioning normally. They 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. Thanks to a recent grant from the National Institutes of Health, the two researchers expect soon to begin clinical trials to test this approach.

In the 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. 

They are also monitoring the progress of neuroprotective drugs still in the pipeline that might prove even safer or more effective than the medications they are studying, Robinson says.

If synergy is the story of the therapies Robinson and Jantzie are developing, it is also the story of their collaboration. 

“I think the reason Dody and I have been so successful at this is that we are both very good at our jobs, and we bring complementary strengths to the table,” says Jantzie, an associate professor of pediatrics at Johns Hopkins who has for years run her own lab doing cutting-edge research into the developing brain. “Even when Dody and I were working on opposite sides of the country, we continued to collaborate. It has been that important to us. But I jumped at the chance to come to Johns Hopkins so that we could work in close proximity again. It has really helped move all aspects of the work along, and helped connect me to the clinical side, which makes the lab work better.”

Robinson says, “Hopkins is one of the best pediatric neuroscience environments in the world. Many places are known for excelling in this subspecialty or that subspecialty. We’re exceedingly lucky because we are one of the few places with experts in every possible area, and we’re supported by excellence in related fields, like neuroradiology, not to mention all of the basic science. We’re one of the few places that really has this connection to the research, and bringing the research from the lab to the patients. And it’s a very supportive environment of people working together to achieve similar goals.”

Jantzie agrees. “My work with Dody fits in beautifully here. Not only do we work very well together, we share the same focus. I am not a surgeon, but I wake up every morning thinking about Dody’s patients. This work is about the kids, and it’s been a defining joy in my career.”