Rare Epilepsy: New Treatment Model Identified
- Jude Children's Research Hospital have developed a first-of-its-kind cortical organoid model for Ba5-associated encephalopathy, a rare and devastating brain disorder.The research, published in Science Translational Medicine, explores the...
- Ba5-associated encephalopathy, characterized by impaired brain function, limited developmental progress, and early-onset seizures, currently has no targeted treatment.Existing interventions focus on managing symptoms such as muscle tone deficiencies...
- Jude, noted that some individuals with two partially functioning copies of the gene remain healthy.
St. Jude researchers pioneer a groundbreaking cortical organoid model, offering a ray of hope for those battling Ba5-associated encephalopathy, a devastating rare epilepsy. Their innovative approach has identified potential treatment avenues, a critical advancement as the disease currently lacks targeted therapies. The study dives deep into the developmental defects caused by UBA5 gene mutations, revealing how a boost in the gene’s partially functioning copy could reverse the mutation’s effects. The team observed stunted interneuron growth, which may explain why patients experience seizures. With this news from News Directory 3, scientists are poised to refine treatment strategies, focusing on dosage and delivery methods, giving families more hope. Discover what’s next, as they aim to establish the most effective treatment window.
St. Jude researchers Model Rare Encephalopathy, Paving Way for Potential Treatments
Updated June 18, 2025
Memphis, Tenn. — Scientists at St. Jude Children’s Research Hospital have developed a first-of-its-kind cortical organoid model for Ba5-associated encephalopathy, a rare and devastating brain disorder.The research, published in Science Translational Medicine, explores the developmental defects caused by mutations in the UBA5 gene and identifies potential therapeutic avenues.
Ba5-associated encephalopathy, characterized by impaired brain function, limited developmental progress, and early-onset seizures, currently has no targeted treatment.Existing interventions focus on managing symptoms such as muscle tone deficiencies and physical limitations. The condition arises when both copies of the UBA5 gene are mutated, tho one copy often retains partial functionality.
Heather Mefford, MD, phd, of St. Jude, noted that some individuals with two partially functioning copies of the gene remain healthy. “This told us that if we could coax the cells to make enough of the copy that doesn’t work as well, it might be a potential therapy,” Mefford said.
the research team, led by Helen Chen, PhD, formerly of St. Jude, utilized patient-derived induced pluripotent stem cells to grow cortical organoids. These three-dimensional cell cultures mimic brain advancement, allowing researchers to study the disease’s genetic architecture by comparing them to healthy models.
The organoids from patients with Ba5-associated encephalopathy exhibited significant differences. “The patient organoids are smaller, grow slower and have increased but less organized electrical activity,” Mefford said. “This is a key point because most of these patients have seizures that are hard to treat.”
The model revealed stunted growth of GABAergic interneurons, which play a crucial role in preventing hyperactivity in the brain. According to Mefford, this imbalance between neuronal excitation and inhibition may explain the seizures experienced by patients. the team found that boosting the expression of the partially functioning Ba5 gene copy reversed the mutation’s effects, suggesting a potential treatment strategy.
Chen expressed enthusiasm about the initial findings and emphasized the ongoing use of the patient-derived model to refine treatment approaches, focusing on optimal dosage and delivery methods.
Mefford highlighted the critical role of families and advocacy groups in rare disease research. “Having them involved is really impactful,” she said, noting their hopefulness and understanding of the research’s potential to benefit future patients.
What’s next
Researchers plan to further investigate the therapeutic window for treatment and establish the minimum effective dose using the patient-derived model.