Levetiracetam: An antiseizure drug with unique neuroprotective properties

Levetiracetam (LEV) and related racetam anti-seizure drugs possess neuroprotective properties that show therapeutic promise in multiple neurodegenerative disorders. Here, we briefly review LEV’s mechanism, noting its unique interaction with synaptic vesicle protein 2A (SV2A) and its ability to prevent epileptogenesis, which may contribute to its neuroprotective properties. We then discuss recent studies in animal models of disease. LEV improved cognitive function in transgenic mouse models of Alzheimer’s disease and HIV-associated neurocognitive disorder, provided neuroprotection in cellular models of Parkinson’s disease, and reduced infarct volume following stroke and traumatic brain injury in rats. LEV failed to alter the course of multiple sclerosis in mice. In human clinical trials, the effects of LEV are positive but still being investigated; it improved cognitive function in patients with Alzheimer’s disease that exhibited electrographic seizures, improved motor function in patients with Huntington’s disease, and improved dexterity and reduced phasic but not tonic spasticity in multiple sclerosis. Clinical trials evaluating LEV’s potential for neuroprotection are currently underway for Parkinson’s disease. It’s unclear from human studies the degree to which LEV alters the progression of neurodegenerative disease. While not a panacea, LEV affords some neuroprotection in neurodegenerative disorders that exhibit a strong excitotoxic component and its use as an add-on to treatments targeted to primary causes underlying disease should be explored.