Regulation of T-type calcium channel activity by targeting channel trafficking – a novel approach for pain management
Current therapies to manage pain either result in side effects or are insufficient and the associated medical costs and loss of work days come pose a tremendous socioeconomic burden. We recently showed that T-type channel activity is aberrantly regulated in inflammatory and neuropathic pain by the deubiquitinase USP5, and we have begun to explore this mechanism as a new therapeutic avenue based on interfering TAT peptides. We now plan to test our TATpeptides in diabetic neuropathy and inflammatory bowel pain. We also plan to generate additional TAT peptides to enhance efficacy in vivo and validate them at the cellular and whole animal level. Compared with ion channel blockers which often lack specificity, our approach specifically targets a process that is involved in aberrant upregulation of channel activity, while sparing normal channel function, thus reducing the risk of adverse side effects.