Conclusion and Implications
Our findings demonstrate anti-seizure effects of targeting the P2X7R in a human neuronal network model of epilepsy and suggest P2X7R-based treatments may be an effective add-on therapy for controlling drug-resistant seizures.
Keywords
Human derived pluripotent stem cell-(hiPSC)-derived neurons, In vitro model of drug-resistant seizures, P2X7 receptor, ATP, Inflammation
Abbreviations
ASM, anti-seizure medication; C1q, complement component 1q; DAMP, damage-activated pattern; BzATP, 2′,3′-O-(4-benzoylbenzoyl)-ATP; eATP, extracellular ATP; GABA, γ-aminobutyric acid; hiPSCs, human induced pluripotent stem cells; IBI, inter-burst-intervals; IL, Interleukin; P2X7R, purinergic P2X7 receptor; KDE, Kernel density estimation; pNSCs, primitive neural stem cells; PTX, picrotoxin; TNF-α, tumour necrosis factor-α

Bullet point summary:

What is already known

P2X7R expression is increased in epileptogenic tissue in the brains of animal models of epilepsy and epilepsy patients.
P2X7R antagonism can attenuate seizures in animal models.

What this study adds

P2X7Rs are expressed and functional on hiPSC-derived neurons.
P2X7R antagonism reduces drug-refractory seizures in a human epilepsy cell model system under inflammatory conditions.

What is the clinical significance

The findings suggest P2X7R antagonism could be an add-on therapy for patients with drug-refractory epilepsy.