As a pediatric critical care attending, Jennifer Munoz-Pareja, M.D., had always been interested in neuroscience research. When she was hospitalized with a traumatic brain injury (TBI) in 2012, she witnessed firsthand how patients, families, and healthcare providers are largely working in the dark when it comes to caring for patients with TBI.
“I thought, ‘Wow. We really don’t have treatments. Nothing really works for these patients,’” she says.
The knowledge gap is even more severe for children, says Dr. Munoz-Pareja, an associate professor in the Department of Pediatrics at the Miller School of Medicine. She decided to focus her work going forward on improving care for pediatric patients with TBI (pTBI). With support from grants including a pilot award from the Miami Clinical and Translational Science Institute (CTSI), Dr. Munoz-Pareja is developing new tools to advance the diagnosis, prognostication, and treatment of pTBI.
She’s starting by building a biorepository of data from pediatric patients across the state of Florida. Colleagues in Miami, Jacksonville, Gainesville, and Orlando are already on board to collaborate. Following recent IRB approval, she plans to begin enrolling patients at Jackson Memorial Hospital before the summer. With the preliminary data collected through these partnerships, Dr. Munoz-Pareja and her team plan to apply for NIH funding.
Sharing data will help her research team better understand the factors at play during a pTBI. For one, she is looking at how pTBI effects biomarkers of neuronal injury and inflammation in children. These biomarkers have been studied in adults, and one has recently received FDA approval, says Dr.
TBI causes inflammation in the brain that can activate the inflammasome complex, leading to the release of several proteins into the bloodstream. The development of a blood test designed to detect these proteins would be a groundbreaking advancement in care for pediatric patients with traumatic brain injuries. A pTBI biomarker panel could assist clinicians in understanding injury severity, mortality risk, and potentially be used to determine long-term rehabilitation needs, says Dr. Munoz-Pareja.
For children with more severe injuries, including those that require a medically induced coma, a biomarker test would allow doctors to monitor a child’s progress without moving them to the MRI scanner or CT scanner, says Dr. Munoz-Pareja. Patients with less severe injury could avoid unnecessary testing altogether.
“We do have statistically significant values that show us that indeed in the kids with higher TBI severity, the value is much higher and in the kids with less severity, the value is lower, which could easily be used to trend and determine whether things are getting better, perhaps even without imaging,” she says.
In addition to confirming a pTBI diagnosis and tracking a patient’s progress, Dr. Munoz-Pareja also believes determining the amount of inflammasome in the blood may also help doctors make predictions about how a child will fare in the future. “We continue to find that these proteins are indeed elevated, and they correlate with a negative outcome,” she says.
The ultimate hope is that better testing options early on could lead to the development of therapeutics to mitigate the cascade and reduce the severity of the outcomes following a pTBI, says Dr. Munoz-Pareja. She says the question becomes, “If we know that this protein is increased in the brain significantly and is associated with worse outcomes and severity, could we find a drug to block this inflammation pathway and improve the outcome for these children?”
In short, a more precise look at what is happening in the body following a pTBI would allow physicians and families to be more knowledgeable and confident in their choices as they move forward with a plan of care.
Dr. Munoz-Pareja’s work is supported by a long list of colleagues and champions at the University of Miami Miller School of Medicine, including W. Dalton Dietrich, PhD., scientific director at The Miami Project to Cure Paralysis, as well as associate director of the Miami CTSI and leader of the CTSI’s Pilot Program.
“Dr. Munoz-Pareja is on track to become a prominent presence in the field of pTBI,” says Dr. Dietrich, who is also the Miller School’s senior associate dean for Discovery Science, and co-director of the Institute for Neural Engineering. “The measurements of specific inflammatory mediators will help identify novel therapeutic targets to protect the brain from progressive injury and promote functional recovery in this highly vulnerable population.”
Munoz’s group is also developing more robust testing techniques to assess children following a pTBI diagnosis. The test would go beyond the current cognitive battery to determine how a child is doing academically, socially, and psychologically following their injury.