Grant: Proof of Principle Program - Phase I

In Canada, smoking is the greatest preventable cause of illness, disability and premature death, causing more than 45,000 deaths per year. As well, links between health problems such as cancer, heart disease and respiratory disease, and exposure to second-hand smoke are well established (From Health Canada). Despite the harmful consequence, it is difficult to quit smoking due to its addictive nature as well as its positive effects on mood and cognition, which are strong reinforcements for smokers that contribute to their addiction. Nicotine, the main alkaloid found in tobacco, is the key addictive component that drives continued use through activation of their specific receptors. Although several medications are available, including a wide range of nicotine-replacement therapies (NRTs), bupropion (Wellbutrin/Zyban; GlaxoSmithKline) and the recently approved alpha4beta2 nAchR partial agonist varenicline (Chantix/Champix; Pfizer), at best only about a fifth of smokers are able to maintain long-term (12 months) abstinence with any of these approaches. Notably, most of the FDA-approved medications for nicotine dependence have not been developed using the typical pharmaceutical industry approach of drug discovery to preclinical testing to clinical trials, a situation resulted from lack of unique therapeutic targets for nicotine addiction. Thus, our present proposal aims at validating the ability of our newly developed protein peptide to block nicotine relapse through intravenous injection, as we have confirmed that the identified peptide is able to block nicotine relapse in the animal model of nicotine relapse through intraventricular route.