Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia

摘要: In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding sodium channel Nav1.7 expressed peripheral nervous system plays a critical role IEM. A gain-of-function mutation this leads to aberrant sensory neuronal activity and extreme pain, particularly response heat. Five patients IEM were treated new potent selective compound that blocked resulting decrease heat-induced most patients. We derived induced pluripotent stem cell (iPSC) lines from four five subjects produced neurons emulated phenotype hyperexcitability responses heat stimuli. When we compared severity iPSC-derived neurons, saw trend toward correlation for individual mutations. The vitro was sensitive blockers, including test agent. Given importance peripherally channels many our approach may have broader utility wide range conditions.