Phase I established that the conantokins, a novel class of N-methyl-D-aspartate (NMDA) receptor antagonists isolated from Conus marine snail venoms, display a unique broad-spectrum anticonvulsant profile at doses that were devoid of motor impairment. Conantokins potently blocked both chemically- and electrically-induced seizures in rodents, suggesting potential efficacy in human seizure disorders including generalized tonic-clonic and generalized absence/myoclonic seizures. The protective index of conantokins was superior to other NMDA antagonists described to date. These striking findings indicate that conantokins are potentially useful therapeutics for therapy-resistant seizure disorders. Phase II will focus on development of conantokin-G, the lead candidate and prototype identified in Phase I, or an analog, as a potential therapeutic agent for therapy-resistant epilepsy. We will fully define the anticonvulsant spectrum of the compound by further assessing its efficacy against corneal-, and amygdala-kindled and ( -butryl lactone (GVL)-induced spike-wave seizures. We will obtain the supporting data necessary for submission of an IND to the FDA. Phase II studies will result in a mechanistically-unique lead compound for clinical trials that may provide a significant advance for the treatment of uncontrolled seizures.
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