Novel first-in-class voltage-gated calcium channel positive allosteric modulators that stabilize the open state of the channel and have therapeutic potential to treat a variety of neuromuscular conditions

We have recently developed a series of novel, first-in-class, voltage-gated calcium channel (VGCC) positive allosteric gating modifiers that are selective for the types of VGCCs that regulate transmitter release at neuromuscular synapses (Ca_V2). These small molecules do not cross the blood-brain barrier well and have been shown to have therapeutic potential to treat a variety of neuromuscular diseases characterized by weakness of presynaptic origin (Lambert-Eaton myasthenic syndrome (LEMS) and Spinal Muscular Atrophy (SMA).