The First Sign
When Amber Freed’s twins were one month old, she noticed something wasn’t right.
During tummy time, Riley lifted her head. Maxwell couldn’t. He would stare at his finger for long stretches—not seconds, but hours—and Amber found herself returning to the pediatrician with the same quiet conviction that something deeper was at play. “Mother’s intuition is loud,” she would later say.
By 2018, that instinct led to a diagnosis: a mutation in Maxwell’s SLC6A1 gene.
Mother’s intuition is loud.
Amber FreedMaxwell’s Mother
SLC6A1 is a neurodevelopmental disorder that disrupts the transport of GABA, one of the brain’s primary inhibitory neurotransmitters. Mutations can result in epilepsy, intellectual disability, autism spectrum disorder, hypotonia, and gait abnormalities. Many variants—including Maxwell’s—result in loss of function, meaning the protein is shortened or degraded and cannot effectively transport GABA across cell membranes.
“It’s been known since the 1990s that SLC6A1 produces a transporter that transmits an important neurotransmitter called GABA across the membrane of cells,” explains Allison Bradbury, PhD, Principal Investigator in the Jerry R. Mendell Center for Gene Therapy at the Abigail Wexner Research Institute at Nationwide Children’s Hospital, and Associate Professor in the Department of Pediatrics at The Ohio State University. By the time of Maxwell’s diagnosis, only a few dozen patients had been described in the medical literature. A small but growing body of research had defined the condition’s clinical spectrum, but there was no established treatment pathway and no program designed to intervene at the genetic level.
Amber began contacting researchers across the country. The scientific consensus was clear: in principle, SLC6A1 was a candidate for gene replacement therapy. If a functional copy of the gene could be delivered to the appropriate cells, it might restore protein function and potentially alter disease progression.
Ultra-rare diseases face structural barriers: patient populations are small, making traditional large-scale clinical trials less feasible; industry investment is often limited; and academic programs often stall between proof-of-concept and human treatment.
That’s when Ohio entered the picture.
From Bench to Bedside
When Amber searched for an academic partner capable of advancing a gene therapy from concept to clinic, Nationwide Children’s Hospital in Columbus consistently surfaced as a leader.
Dr. Bradbury had just relocated from the University of Pennsylvania to establish her independent lab at Nationwide Children’s in early 2020.
There are a lot of places you can work in the lab and develop a gene therapy, but there aren’t many places where you can actually take that gene therapy from the bench all the way to the bedside.
Allison M. Bradbury, MS, PhDPrincipal Investigator, Nationwide Children’s Hospital
Nationwide Children’s had already advanced multiple pediatric gene therapies into clinical trials and achieved two FDA market approvals: Zolgensma for spinal muscular atrophy and Elevidys for Duchenne muscular dystrophy. The translational pathway—from preclinical research to regulatory engagement to clinical delivery—had been established.
“The path had been paved,” Bradbury continues.
Unlike many ultra-rare programs that fragment across institutions, Nationwide Children’s houses the full continuum—preclinical labs, in-house animal and safety testing, regulatory expertise, clinical leadership, and off-site manufacturing through Andelyn Biosciences.
“For our SLC6A1 work, we kept research activities in-house,” Bradbury notes. “We didn’t use a contract research organization (CRO) for any of our proof-of-concept or safety studies.”
for Gene Therapy at Nationwide Children’s Hospital.
Rigorous by Design
The therapeutic strategy was gene replacement.
Researchers packaged a healthy copy of SLC6A1 into an adeno-associated virus (AAV), removing the virus’s own genes and inserting the functional gene. The therapy was designed for delivery directly into the cerebrospinal fluid, bypassing the blood-brain barrier and reducing off-target exposure.
“We’re not getting rid of the broken DNA,” Bradbury explains. “We are just replacing it with a functional copy of a healthy working gene.”
Researchers developed multiple versions of the viral delivery system, refining how the therapy would target the brain’s key cell types and determining the appropriate dose. The goal was to identify a therapeutic threshold—enough to restore gene function without overstimulating a sensitive neurotransmitter system.
After demonstrating improved motor coordination and reduced seizures in preclinical testing, the team began formal discussions with the U.S. Food and Drug Administration. Through a pre-IND process—a step that precedes submission of an Investigational New Drug (IND) application—they aligned on safety requirements, manufacturing standards, and trial design before requesting authorization to begin human clinical studies.
“You really have to stick to doing rigorous science,” Bradbury says. Cutting corners, she notes, could jeopardize not only one program but the broader field of gene therapy.
Clinical Leadership & Coordinated Execution
As the program advanced toward clinical implementation, Emily C. de los Reyes, MD—attending pediatric neurologist at Nationwide Children’s Hospital and Professor of Clinical Pediatrics and Neurology at The Ohio State University College of Medicine—led the clinical protocol development.
“I’ve already developed some protocols that have gone to FDA,” she explains, reflecting on prior experience guiding rare disease trials through regulatory review.
At Nationwide Children’s, that work does not occur in isolation.
We have a team approach. A clinician doesn’t need to meet with external personnel to consult on regulatory transitions from pre-IND to IND. We just have to make phone calls or walk across the street.
Emily C. de los Reyes, MDAttending Pediatric Neurologist, Nationwide Children’s Hospital
From immune monitoring protocols to ICU readiness, prior gene therapy experience informed each layer of risk mitigation. “The whole hospital pretty much knows what to do,” de los Reyes says.
The Investigational New Drug (IND) application required coordinated work across research, regulatory, manufacturing, and clinical teams. As Dr. Bradbury notes, “If you can’t put the package together to convince the FDA that you’ve done the work in the right manner, then you can’t translate the therapy.”
Building on earlier work that began in 2018, the Ohio-based SLC6A1 effort progressed from early research to clinical readiness in just over five and a half years, culminating in dosing in September 2025.
Hospital.
Five and a Half Years in Five Minutes
In September 2025, Maxwell Freed received an investigational therapy at Nationwide Children’s. He is the first patient in the world to receive gene replacement therapy for SLC6A1.
The administration itself took just minutes—a carefully delivered dose into the cerebrospinal fluid under controlled clinical conditions. Years of laboratory work, regulatory review, manufacturing preparation, and clinical coordination were distilled into a single infusion.
For Amber, the milestone was deeply personal. She later described noticing small but meaningful changes in Maxwell—greater coordination, increased stamina, growing independence. As Dr. Emily de los Reyes emphasizes, the program remains a clinical trial, and outcomes continue to be monitored within regulatory parameters.
But the moment reflected something larger: a foundation-supported, academically driven ultra-rare gene therapy advancing from hypothesis to human treatment within a single, integrated ecosystem.
“Ultra-rare diseases really have unique challenges,” Dr. Allison Bradbury says. Small patient populations limit traditional funding pathways, and many programs depend on foundation support. Advancing SLC6A1 required sustained institutional commitment—the willingness to invest in the science, the manufacturing, and the regulatory work long before a clinical milestone was guaranteed.
At Nationwide Children’s, that commitment is backed by infrastructure:
- A gene therapy operations unit with more than 40 full-time staff, supporting researchers with regulatory, operational, and administrative coordination so scientists can remain focused on the science
- In-house preclinical and safety testing
- Available Good Manufacturing Practice (GMP) manufacturing—the FDA-regulated standard required for clinical-grade therapies—through Andelyn Biosciences, also located in Ohio.
- A regulatory team experienced in multiple IND submissions
“Really, all of those people and all of those resources coming together…made it feasible,” Bradbury says.
Precision Medicine, Built in Ohio
For Dr. de los Reyes, the SLC6A1 program represents more than a single clinical case.
“The world of precision medicine is opening up for our children with rare disorders,” she says—not as a distant possibility, but as a direction already taking shape.
Ohio’s pediatric gene therapy platform—built on research depth, regulatory experience, in-state manufacturing, and coordinated clinical care—continues to advance programs that might otherwise stall in smaller or fragmented systems.
What began with Maxwell Freed’s diagnosis is now part of a broader model: identify a genetic target, build the preclinical foundation, align with regulators, and deliver treatment within a single ecosystem.
“My hope,” Dr. de los Reyes adds, looking ahead, “is that… we can name a rare disorder and say, ‘Oh, we’ve completely treated that.’”
For Maxwell, that future began with a dose. For Ohio, it reflects a trajectory in which genetic discovery, clinical rigor, and coordinated infrastructure continue to converge—enabling the next breakthrough, and the next child.
