Intranasal nanoparticle-encapsulated neuropeptide Y provided robust seizure protection across multiple seizure models and reduced spontaneous seizures in a Dravet syndrome mouse model.
3 seizure models protectedby intranasal nanoparticle-NPY, plus reduced spontaneous seizures in Dravet syndrome mice — all through non-invasive nasal delivery
What the researchers found
Intranasal administration of nanoparticle-encapsulated NPY (NP-NPY) provided robust protection against 6 Hz-, pentylenetetrazole-, and hyperthermia-induced seizures in two mouse models of SCN1A-derived epilepsy. In Scn1a+/- mutant mice (a Dravet syndrome model), NP-NPY treatment reduced spontaneous seizure frequency.
The nanoparticle formulation overcomes a critical barrier in neuropeptide therapeutics: delivering a 36-amino-acid peptide to the brain through a non-invasive intranasal route, bypassing the blood-brain barrier without requiring surgery or gene therapy.
Why it matters
Dravet syndrome is a severe childhood epilepsy with high drug resistance — current medications often fail. NPY has been known to suppress seizures, but until now could only be delivered through invasive methods. This intranasal nanoparticle approach makes NPY brain delivery practical, potentially opening a new treatment avenue for one of the most devastating forms of childhood epilepsy.
How the study worked
Researchers developed a nanoparticle formulation to encapsulate NPY and administered it intranasally to mouse models of SCN1A-derived epilepsy. They tested seizure resistance using three different induction methods (6 Hz electrical stimulation, pentylenetetrazole chemical induction, and hyperthermia). They also monitored spontaneous seizures in Scn1a+/- Dravet syndrome model mice. Gene expression analysis compared NPY and NPY receptor levels in mutant and wild-type hippocampi.
What this study cannot tell us
All experiments were in mice; human Dravet syndrome is more complex and variable. The duration of seizure protection after a single intranasal dose and the need for repeated dosing are not detailed. Long-term safety of intranasal nanoparticle administration to the brain needs assessment. The nanoparticle formulation's stability, shelf life, and manufacturing scalability are not discussed.
How to read the evidence
This is a preclinical study using multiple mouse models of SCN1A-derived epilepsy, including a Dravet syndrome model. Testing across multiple seizure induction methods strengthens the evidence, but human translation is still needed.
When this study was published
Published in 2026 in Epilepsia, a leading epilepsy journal, this is a very recent study presenting a novel delivery approach for neuropeptide-based seizure therapy.
The bigger picture
This study addresses two major challenges simultaneously: the difficulty of treating drug-resistant epilepsy and the challenge of delivering peptide therapeutics to the brain. Intranasal nanoparticle delivery could become a platform technology for multiple brain-active peptides, not just NPY. For the epilepsy field, it demonstrates that endogenous neuropeptides can be harnessed as therapeutics when delivery barriers are overcome.
Questions still open
- How long does seizure protection last after a single intranasal dose of NP-NPY?
- Could this nanoparticle delivery platform be used for other anti-seizure neuropeptides like galanin or somatostatin?
- Would NP-NPY be effective in other drug-resistant epilepsy types beyond SCN1A-derived forms?
Common questions
What is Dravet syndrome and why is it hard to treat?
How does a nasal spray deliver medicine to the brain?
Read the original research
Nanoparticle-encapsulated neuropeptide Y provides robust seizure protection in SCN1A-derived epilepsy.
Epilepsia, 67(1), 424-436
Citation
Reed, Samantha L; Aiani, Lauren M; Faiz, Eesha; Adediran, Emmanuel; Benveniste, Morris; Murnane, Kevin S; D'Souza, Martin; Escayg, Andrew; Wong, Jennifer C. (2026). Nanoparticle-encapsulated neuropeptide Y provides robust seizure protection in SCN1A-derived epilepsy.. Epilepsia, 67(1), 424-436. https://doi.org/10.1111/epi.18649