Potassium channel inhibitors for symptomatic treatment of multiple sclerosis

Multiple sclerosis (MS) is caused by demyelination of nerve axons. A widely-used symptomatic treatment for MS is 4-aminopyridine (dalfampridine, Ampyra), a potassium channel inhibitor that is believed to improve motor function by inhibiting potassium channels that are exposed by demyelination and disrupt propagation of action potentials. Dalfampridine is poorly selective among various kinds of potassium channels and as a result is pro-epileptic and has a very narrow therapeutic index. We will screen for more selective and more potent inhibitors using an automated patch clamp instrument and then work with the Therapeutics Translator team to do medicinal chemistry optimization of initial hits to develop optimally potent and selective compounds.