Sustained-release fampridine for multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system of unknown cause in which neurological impairment and disability result from demyelination and axonal loss. Physiologically, myelin loss leads to changes in axonal ion channels that cause conduction failure. Axonal loss leads to a reduction in signal strength in neuronal pathways. Fampridine (4-aminopyridine) is a potassium channel blocker that can increase action potential duration and amplitude, leading to improved conduction in demyelinated nerve fibers and to increased neurotransmitter release at synaptic endings. Fampridine treatment can improve ambulation in some MS patients, but can also cause seizures and other side effects. Pharmacokinetic studies show that improvement in neurological deficits is primarily related to the total fampridine dose, while seizure induction is related to peak serum levels. To reduce side effects, a slow-release (SR) formulation of fampridine was developed. Two Phase III studies of fampridine SR have now shown that treatment can improve leg strength and walking speed in patients with MS; a new drug application has been filed with the US FDA.