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.