Nicotine degradation in smokers: will a new and potent enzymatic approach work where nicotine vaccines have failed?

Abstract

Smoking and tobacco use continue to be the largest preventable causes of death. Although there are current pharmaceutical and behavioural therapies, the one-year sustained quit rate of these therapies is only 20-25% at best. Recently, an alternative biotherapeutic strategy has been proposed: enzymatic degradation of nicotine in the bloodstream preventing accumulation in the brain. The bacterial enzyme NicA2 oxidizes nicotine into pseudo-oxynicotine, a non-addictive compound already found in smokers. Proof-of-concept animal studies have shown that NicA2 can rapidly reduce the levels of nicotine accumulating in the brain after intravenous nicotine dosing, and NicA2 has shown to have efficacy in a continuous nicotine access self-administration rat model.Enzymatic elimination of nicotine upon smoke inhalation to combat tobacco addiction is an innovative therapeutic concept. However, it is in line with recent clinical studies demonstrating that reduction in nicotine content in cigarettes (to 2.5% of normal levels) lead to significant reduction in the number of cigarettes smoked and higher smoking cessation rates compared to a control group smoking normal nicotine level cigarettes. Enzymatic degradation of nicotine appears to be more potent than nicotine-specific antibodies or vaccines for reducing nicotine distribution to brain, and if this proves to be the case in humans, it could also be more effective for enhancing smoking cessation rates and succeed where nicotine vaccines have failed thus far. The work reviewed in this article constitutes promising initial steps towards an urgently needed new effective treatment strategy in smoking cessation therapy.

State of Oral Health of Women in Rural Areas in An Underdeveloped Country: A Prospective Observational Descriptive Study

“…Nicotine degradation in the blood can be achieved using the bacterial enzyme NicA2. NicA2 is an enzyme found in Pseudomonas putida and Arthrobacter nicotinovorans that can degrade nicotine through enzymatic processes [15]. It oxidizes nicotine into non-addictive compounds, such as pseudo-oxynicotine and 2,6-dihydroxypseudooxynicotine, which can prevent the accumulation of nicotine in the brain [16].…”