In January, we announced our 2019 Innovator Award grantees. The Innovator Award is designed to provide seed funding for bold and innovative work with the potential to transform hydrocephalus research. In this second installment of our Meet the Innovator Award Grantees Blog Series, we interviewed Dr. Brandon A. Miller, one of four scientists who received an Innovator Award grant. Dr. Miller is an Assistant Professor in the Department of Neurosurgery at the University of Kentucky. For his project, he will test an antioxidant drug therapy that could reduce nerve injury caused by a brain bleed. The drug is already FDA approved for other uses and could improve brain function for premature babies who are at risk of developing posthemorrhagic hydrocephalus.
What sparked your interest in hydrocephalus research?
During my pediatric neurosurgery fellowship is when I really began to understand and see children with hydrocephalus over a longer stretch of time and realized we have a lot of opportunity to improve their care. Then when I started my job at the University of Kentucky and was given the opportunity to start a lab in the Spinal Cord and Brain Injury Research Center, I realized that it was the perfect place to study brain injury in intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus. I found my colleagues were very interested in learning about the this disease and helping to lend their expertise.
What do you find most interesting about hydrocephalus research?
There are a lot of parallels we’ve seen in our hydrocephalus data when we compare it to data from traumatic brain injury. We think a lot of the same mechanisms in play in neonatal brain have been more well studied in other diseases and therefore we can use some of this prior work to guide us.
How long have you been researching hydrocephalus?
About two and a half years.
What do you hope to learn from your research funded by the Innovator Award Grant? What questions do you hope your research will answer?
We’re trying to use an antioxidant therapy to reduce brain injury after IVH and in hydrocephalus. The reason we’re doing this is because we’ve seen oxidative stress in the brain after IVH and experiments in a cell culture system of developing white matter showed that this drug can protect the cells from some of the deleterious effects of hemoglobin. So we’re essentially trying to scale up from a drug that we found to be promising in our cell culture system and use it in a rodent model so that eventually it could be used in clinical trials. This drug has been clinically approved as an antidepressant but it hasn’t been used for this application yet.
What makes your project unique?
We are focusing more on intrinsic brain injury and the consequence that IVH has on cells in the brain, apart from just the development of hydrocephalus. Our model creates hydrocephalus as well but I think that the amount of fluid in the brain is not the only important outcome after IVH and a lot of disability that patients with hydrocephalus have is not just from fluid but from brain injury caused by the brain bleed. We can treat hydrocephalus with a shunt but we know that a lot of people, even when their hydrocephalus is well treated, are not completely healed so the question is what else is going on in those patients? This is where I think there are lots of opportunities to improve care.
How important is HA’s Innovator Award grant for your project?
Having the Innovator Award grant means that I can complete the project and direct resources in my lab toward this project. We did cell culture studies that show promise but animal studies are more expensive, so having the Innovator Award grant helps us take that intermediate step to bring things toward a clinical trial. It’s a large financial commitment to get good preclinical data, so now we will be able to proceed with that.
What is the long-term plan for the project?
My hope is to take this drug, or other drugs we’re studying, into clinical trials in our neonatal intensive care unit (NICU) where we have experience in clinical trials that have looked at neurodevelopmental outcomes and where we have the capacity to do long-term neurocognitive testing in our NICU graduates. Here at the University of Kentucky, we have a NICU Graduate Clinic that follows kids until about 3 years of age. We have the mechanism here to study young patients and collect a wealth of clinical data so now we have to focus on using this opportunity to test the most promising treatments in clinical trials.