Unmet NeedAbnormal behavior of sodium (Nav) channels is linked to a variety of epilepsy syndromes, movement disorders, and neuropathic pain. While researchers continue to elucidate the roles of different Nav channel isoforms within a variety of neurological disorders, current therapeutics influence numerous Nav channel isoforms, resulting in off-target side effects. Development of therapeutic compounds capable of targeting specific Nav channel isoforms is important for treatment of Nav-associated disorders. Technology OverviewThis inventor identified strongly anti-epileptic triazole-derived compounds that specifically act on Nav1.1, useful for the efficient treatment of Lennox-Gastaut Syndrome, related epileptic disorders, and diseases such as cognitive impairment without seizures and migraine. Moreover, the inventor was the first to uncover a new role for Nav1.1 in mechanical pain (allodynia) and found triazole-derived compounds that strongly attenuate pain in multiple animal assays. The inventor has designed structural derivatives of this molecule that specifically modulate Nav1.1 and Nav1.6 channel isoforms, and developed an assay for screening the effects of drug compounds on Nav channel function, thus presenting valuable new therapeutics and tools for treatment of a variety of neurologic disorders.
Stage of DevelopmentPre-clinical data are available in three independent seizure models for most compounds and two animal models for pain. Plasma pharmacokinetics, brain and CSF distribution of the lead compound in mice are also available (IV, IP, and oral). Inventors have confirmed compound selectivity for Nav1.1 and Nav1.6 and identified a novel mechanisms of action that helps explain the lack of observed side-effects (as tested in mice).
PublicationsACS Chem Biol 2014JGP 2015Nature 2016
