Treatment of Chemotherapy-Induced Peripheral Neuropathy via Genetic Repression of Sodium Channels

Project Summary Abstract The goal of this project is to develop a therapeutic product that relieves chemotherapy induced peripheral neuropathyCIPNin a non permanentnon addictive and long lasting manner to improve the quality of life of cancer patientsCurrently more thanmillion Americans andbillion people worldwide suffer from chronic painVoltage gated sodium channels transmit pain signals in nociceptive neuronsNine genes have been identifiedeach having unique properties and tissue distribution patternsGenetic studies have correlated a rare hereditary loss of function mutation in one channel isoformNaVwith a genetic disorder known as Congenital Insensitivity to PainCIPIndividuals with CIP are not able to feel pain whatsoever and they do not present any significant secondary alterationThusselective repression of NaVshould recapitulate the phenotype of CIPHoweverthe high homology of human NaV proteinshave frustrated most efforts to develop selective inhibitorsWe have developed a non permanent gene therapy to target pain that is non addictivebecause it targets a non opioid pathwayhighly specificonly targeting the gene of interestand long term lastingaroundweeks in our preliminary assays in miceDuring this Phase I SBIRwe willoptimize the in vitro targeting of NaValong with targeting NaVand NaVsince these channels are also responsible for the transmission of pain signalsevaluate the new targets in vivo in a chemotherapy induced peripheral neuropathyCIPNmodel and determine whether there are any sex differences in efficacy of the therapeuticandperform preliminary safety and toxicology studies in miceAt the end of Phase Iwe will know the potencyspecificityand safety of our optimized gene therapy and will apply for a Phase II SBIR grant to perform IND enabling toxicology studiesOur goal is to advance this therapy forward into the clinicto provide an alternative treatment to opioids for cancer patients in pain Project NarrativeNavega Therapeuticsproposal aims to investigate the contribution of NaVNaVand NaVvoltage gated sodium channels in the pain induced by chemotherapeutic agentsThis study will improve our understanding of the mechanisms underlying voltage gated sodium channels in chemotherapy induced peripheral neuropathy and may lead to promising candidates to improve the quality of life of cancer survivors