title: New calcium channel agonists as potential therapeutics in Lambert-Eaton myasthenic syndrome and other neuromuscular diseases.
abstract: Lambert-Eaton myasthenic syndrome (LEMS) causes neuromuscular weakness as a result of an autoimmune attack on the calcium channels that normally regulate chemical transmitter release at the neuromuscular junction. Currently there are limited treatment options for patients with this and other forms of neuromuscular weakness. A novel, first-in-class calcium channel agonist that is selective for the types of voltage-gated calcium channels that regulate transmitter release at neuromuscular synapses has recently been developed. This compound (GV-58) slows deactivation (closing) of the channel, resulting in a large increase in total calcium entry during motor nerve action potential activity. This new calcium channel agonist is currently being evaluated for the treatment of neuromuscular weakness. Potential applications include development as single therapeutics, or for combination treatments.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Tyler B
authors.initials: TB
authors.lastname: Tarr
authors.forename: Guillermo
authors.initials: G
authors.lastname: Valdomir
authors.forename: Mary
authors.initials: M
authors.lastname: Liang
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Meriney
mesh_terms: D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy*; D009468:Neuromuscular Diseases / Q000188:drug therapy*; D011687:Purines / Q000627:therapeutic use*; D000077546:Roscovitine; D013876:Thiophenes / Q000627:therapeutic use*
chemical_list: D002120:Calcium Channel Agonists; C583131:GV-58 compound; D011687:Purines; D013876:Thiophenes; D000077546:Roscovitine