Grant: CIHR Fellowship

Opioid medications are widely used in pain management but are highly addictive and present the severe side-effect of respiratory depression that can be lethal with overdose. The current epidemic of opioid-related overdoses results in over 4,000 deaths every year in Canada, and is responsible for thousands of emergency visits, therefore causing a severe social, medical, and financial burden. The development of safe pain therapies, i.e. pain treatments without the side-effect of respiratory depression and with reduced addictive properties, has been hindered by the absence of efficient drug discovery platforms. This project proposes a paradigm shift by focusing on discovering new molecular targets and drug candidates with reduced side-effects, i.e. respiratory depression and addition. The current targeted mutagenesis and drug discovery approaches to identify new molecular targets and drug candidates are limited because they use complex animal models which are not efficient at a larger scale. Here, I propose to use established zebrafish models of respiratory depression, analgesia, and addiction to perform gene and drug screening. The opioid system, respiratory, and nociceptive circuits in zebrafish present high homologies to mammals, and zebrafish are amenable models to perform drug screening. I will use targeted mutagenesis with CRISPR/cas9 to efficiently identify molecular targets. I will test libraries of repurposed drugs focused on a variety of targets identified by our team. This multidisciplinary proposal is unique because it will quickly identify therapeutic solutions to reduce the risks, morbidity, and mortality associated with opioid drugs.