GV-58

GV-58 is a small molecule gating modifier that acts as a positive allosteric modulator of Cav2-type voltage-gated calcium channels, specifically the P/Q-type (Cav2.1) and N-type (Cav2.2) channels. By slowing the deactivation of these channels, GV-58 increases the duration of calcium influx into presynaptic terminals during an action potential, which enhances the quantal content of neurotransmitter release at the neuromuscular junction (NMJ). Developed primarily by researchers at the University of Pittsburgh and the University of Southern California, GV-58 is being investigated as a potential therapeutic for neuromuscular diseases characterized by synaptic weakness, including Amyotrophic Lateral Sclerosis (ALS) and Lambert-Eaton Myasthenic Syndrome (LEMS). Preclinical studies in ALS mouse models have demonstrated that chronic administration can delay disease progression, maintain synapse innervation, and improve end-plate potential amplitude.