AAV-mediated delivery of neuropeptide Y (NPY) and Y2 receptor to hippocampus reduced seizures in both rapid kindling and genetic epilepsy rodent models, with successful MRI-guided delivery to baboon hippocampus and no adverse events.
Baboon brain successfully reachedNPY gene therapy reduced seizures in 2 rodent models AND achieved MRI-guided delivery to baboon hippocampus with no adverse events—a critical step toward human clinical trials
What the researchers found
SPK100.NPY-Y2R: ↓neuronal activity in cultures + slices. ↓Seizure progression/duration (rat kindling). ↓Spontaneous seizures (genetic mouse model). MRI-guided delivery → successful baboon hippocampus transduction. No adverse events. Non-human primate step completed.
Why it matters
30% of epilepsy patients resist all current drugs. NPY gene therapy could provide lasting seizure control from a single treatment, and successful baboon delivery brings it closer to human trials.
How the study worked
In vitro: rat cortical cultures, mouse hippocampal slices. In vivo: rat rapid kindling, synapsin triple KO mice spontaneous seizures. Non-human primate: MRI-guided CED to baboon hippocampus.
What this study cannot tell us
Rodent models. Baboon delivery confirmed but no seizure testing in primates. Long-term NPY expression durability unknown. Neurosurgical delivery carries inherent risks.
How to read the evidence
Comprehensive preclinical program spanning in vitro, multiple rodent models, and non-human primate delivery. Strong translational evidence.
When this study was published
Published in 2025.
The bigger picture
NPY gene therapy represents a potential cure for drug-resistant temporal lobe epilepsy—the most common type. A single neurosurgical procedure delivering lasting NPY expression could replace lifelong medication or invasive surgery.
Questions still open
- When will human clinical trials of AAV.NPY-Y2R begin?
- How long does NPY expression persist from a single AAV delivery?
- Would ectopic NPY expression cause appetite or other side effects?
Common questions
Could gene therapy cure epilepsy?
How is NPY gene therapy different from anti-seizure drugs?
Read the original research
AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.
Molecular therapy : the journal of the American Society of Gene Therapy, 33(9), 4239-4258
Citation
Terzic, Barbara; Melin, Esbjörn; Fagergren, Pernilla; Dobry, David; Cattaneo, Stefano; Giupponi, Iris; Bettegazzi, Barbara; Simonato, Michele; Agerman, Karin; Kokaia, Merab; Moon, Lawrence; Ramsburg, Elizabeth. (2025). AAV-mediated gene therapy for focal epilepsy by expressing neuropeptide Y and Y2 receptor in rodent and non-human primate hippocampus.. Molecular therapy : the journal of the American Society of Gene Therapy, 33(9), 4239-4258. https://doi.org/10.1016/j.ymthe.2025.06.019