FDA Clears First FOXG1 Gene Therapy for Clinical Trials in Rare Neurodevelopmental Disorder
Key Insights
The FDA has approved an Investigational New Drug application for FRF-001 (search), the first FOXG1 (search) AAV9 gene replacement therapy designed to treat FOXG1 syndrome (search), a rare neurodevelopmental disorder affecting one in 30,000 individuals worldwide.
Developed by University at Buffalo researchers Soo-Kyung and Jae Lee, whose daughter has FOXG1 syndrome (search), the therapy delivers a functional copy of the FOXG1 (search) gene using an adeno-associated virus 9 vector.
The upcoming first-in-human clinical trial will be independently sponsored by the FOXG1 Research Foundation (search), which has secured $14.5 million through its "Yes, They Can" campaign.
The U.S. Food and Drug Administration has cleared FRF-001 (search), a viral gene therapy developed at the University at Buffalo, to begin clinical trials for FOXG1 syndrome (search), a rare neurodevelopmental disorder characterized by cognitive and physical disabilities and epilepsy (search). The approval of the Investigational New Drug application marks a significant milestone for the first FOXG1 (search) AAV9 gene replacement therapy targeting the underlying genetic cause of this devastating condition.
Breakthrough Gene Therapy Approach
FRF-001 (search) was developed by UB biologists Soo-Kyung and Jae Lee, who direct the FOXG1 (search) Research Center at UB and whose personal connection to the disease stems from their daughter's diagnosis with FOXG1 syndrome (search). The therapy works by delivering a functional copy of the FOXG1 gene using an adeno-associated virus 9 (AAV9) vector, directly addressing the genetic root cause of the disorder.
"Reaching a clinical trial reflects the extraordinary commitment of the FOXG1 (search) community, the families who never stopped believing and the incredible support we've received from UB," said Soo-Kyung Lee, PhD, SUNY Empire Innovation Professor and director of the FOXG1 Research Center. "This clinical trial is an important step toward turning their hope into real therapies."
Understanding FOXG1 Syndrome
FOXG1 syndrome (search) results from mutations in the Forkhead Box G1 (search) gene, identified as one of the most critical genes for early brain development. While the condition is rare, affecting approximately one in 30,000 individuals worldwide, the FOXG1 (search) gene has been linked to autism spectrum disorder (search) and certain cancers, suggesting potential broader therapeutic applications for FOXG1-targeted treatments.
The Lees' daughter, Yuna, was diagnosed with the disorder in 2012 at age 2, prompting the couple to redirect their research focus from master regulator genes to studying this specific condition. They joined UB in 2019 and established the FOXG1 (search) Research Center in 2024 with support from the UB Office of Research, Innovation and Economic Development, as well as the FOXG1 Research Foundation (search).
Promising Preclinical Results
Previous research by the Lees demonstrated that FRF-001 (search) can reverse brain abnormalities in mouse models of FOXG1 syndrome (search), particularly in brain regions associated with language, memory, and social interaction. These preclinical findings provided the foundation for advancing the therapy toward human trials.
"As both scientists and parents of a child with FOXG1 syndrome (search), this milestone is deeply personal for us," said Jae Lee, PhD, professor of biological sciences. "It brings hope not only for our daughter, but for all children and families affected by this devastating neurodevelopmental disorder."
Parent-Led Drug Development Model
The upcoming first-in-human clinical trial represents a unique approach to rare disease drug development, being independently sponsored by the FOXG1 Research Foundation (search) rather than a pharmaceutical company. The foundation has secured $14.5 million through its "Yes, They Can" campaign to advance FRF-001 (search) through clinical trials and toward regulatory approval.
According to the foundation, this marks the first instance of a parent-led rare disease nonprofit foundation independently sponsoring its own multi-site, international gene therapy clinical trial. "This is parent-led drug development in action," said Nasha Fitter, co-founder of the FOXG1 Research Foundation (search) and mother to a child with FOXG1 syndrome (search). "We've shown there is another way to advance life-changing therapies for ultra-rare disorders."
The multi-site clinical trial will evaluate the safety and efficacy of FRF-001 (search) in patients with FOXG1 syndrome (search), potentially offering the first targeted treatment option for families affected by this rare neurodevelopmental condition.