Pharmacologically Selective Actuator Module 4-Glycine Receptor (PSAM4-GlyR) (PSAM4-GlyR)

The engineered chemogenetic chloride-conducting ion channel expressed by KRIYA-748 is a synthetic, chimeric ligand-gated ion channel designed for the targeted treatment of trigeminal neuralgia. It is a product of the Pharmacologically Selective Actuator Module (PSAM) platform, specifically a PSAM4-GlyR chimera consisting of a modified alpha7 nicotinic acetylcholine receptor ligand-binding domain fused to a glycine receptor ion-pore domain. This channel is engineered to be selectively activated by varenicline, an FDA-approved small molecule, with high potency and selectivity over endogenous receptors. When expressed in the trigeminal nerve via an adeno-associated virus (AAV) vector, the channel remains inactive until varenicline is administered. Upon binding varenicline, the channel opens to allow the influx of chloride ions, which hyperpolarizes the neuron and suppresses the hyperexcitability associated with paroxysmal pain attacks. This chemogenetic system allows for precise, dose-dependent control of neuronal activity, providing a regulatable therapeutic effect that can be adjusted by the patient. KRIYA-748 aims to provide a one-time gene therapy that can reduce the frequency and severity of pain attacks in patients with medically refractory trigeminal neuralgia. The technology was originally developed by Redpin Therapeutics and later acquired by Kriya Therapeutics for clinical development.

Other names

v-PSAM-GlyRVarenicline-responsive ion channelEngineered chemogenetic chloride channelChimeric alpha7 nAChR-GlyRPharmacologically Actuated Ion Channel

Agonism leading to chloride-mediated neuronal hyperpolarization and silencing