A High Throughput Screen Utilizing Newly Discovered Intramolecular Neuronal Calcium Channel interactions to Discover New Analgesics

Unmet Need
Chronic pain management continues to be a medical and public health imperative. N-type calcium channel blockers, such as FDA approved Prialt® (ziconotide), have been found to have analgesic effects (blocking pain signals from the nerves to the brain) and to work synergistically with opioids. Unfortunately, drugs like Prialt have serious adverse events and must be administered via spinal chord intrathecal infusion, which limits their use to only the most intractable and debilitating pain indications. It is important to identify new therapeutics which provide safer and more effective pain management which work synergistically with, or may even replace, opioids.
 
Technology Overview
Johns Hopkins researchers have developed a high-throughput screening technology capable of detecting new N-type calcium channel blockers with a unique mechanism of action. The inventors have developed high-throughput yeast two-hybrid assay and Fluorescence Resonance Energy Transfer (FRET)-based assay technology that are capable of detecting novel N-type calcium channel inhibitors by measuring the degree that they perturb intermolecular ion channel interactions. Importantly, the type of inhibition detected by these assays is similar to that seen with opioid treatment. The yeast-two hybrid or FRET assay may be used to screen and identify compounds which mimic or potentiate the analgesic effects of opioid treatment.
 
Stage of Development
Yeast-two hybrid and FRET-based high-throughput assays have been developed. A peptide probe has been created that demonstrates N-type calcium channel inhibition similar to that seen with opioid administration.
 
Publications
Agler HL., et al., G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels. Neuron. 2005; 46(6):891-904

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