Tuesday, 18 September 2012

Gene Therapy in Nicotine Addiction


Gene Therapy in Nicotine Addiction


Figure 1-Australian Government (2012)

According to the Australian Institute of Health and Welfare (AIHW), 7.8% of Australia’s total health burden is contributed by tobacco smoking, which is also the highest single preventable cause of Australia’s death and diseases1

Nicotine is a very small molecule found in cigarettes that readily diffuses through skin, lungs and mucous membranes and eventually travels into the bloodstream reaching the brain. The nerve cells in the brain communicate through neurotransmitters which bind to a receptor on the surface of nerve cells. The chemical structure of nicotine is similar to the chemical structure of the neurotransmitter acetylcholine2. Due to the close resemblance in structure, nicotine is capable of activating cholinergic receptors usually stimulated by acetylcholine. These receptors are located in the brain, the heart, muscles, adrenal glands and other peripheral nervous systems and therefore nicotine largely affects the body systemically. Nicotine causes the release of adrenaline, the hormone responsible for fight or flight responses resulting in an increase in heart rate, blood pressure and constricts the blood vessels reducing blood flow to the heart2. It also increases dopamine levels in the brain, a neurotransmitter responsible for feelings of reward and pleasure. The onset of nicotine effects occurs as fast as 10 seconds after inhalation and withdrawal symptoms such as irritability occur when nicotine levels in the body deplete3. Therefore in order to maintain nicotine levels, users resort to continuous smoking which leads to a cycle of nicotine addiction.
Figure 2-Reardon (2012)

Current smoking cessation methods are nicotine patches, gum and prescription medications. Gene therapy may soon be an alternative treatment to suppress nicotine addiction in smokers due to its incredible therapeutic potential. This therapy was tested in mice and showed effective results in controlling nicotine levels reaching the brain. Ronald Crystal of Weill Cornell Medical College achieved this concept by isolating the strongest antibody against nicotine found in a mouse and inserted it into a common carrier used in gene therapy known as adeno-associated virus (AAV)5. This viral vector is a non pathogenic genome comprised of the expression of the full-length, high affinity, anti-nicotine antibody5. This antibody-containing virus was injected into a nicotine-addicted mouse where antibodies were then produced and released into the bloodstream by the mouse. To test the efficiency, researchers administered nicotine equivalent of two cigarettes into the mouse and results showed that 83% of nicotine was bound by the antibodies prior to reaching the brain5. This is more than seven times greater than that in untreated mice. Nicotine concentrations in the brain of the treated mice were reduced to 15% of those in control mice5. The treatment prevented significant nicotine-mediated changes in heart rate, arterial blood pressure and locomotor activity. As well as showing high specificity and high affinity for nicotine, the antibodies were seen to be able to produce monoclonal anti-nicotine antibodies for duration of eighteen weeks in mice5.
Figure 3-Autismspot

Although AAV gene therapy against nicotine addiction has not been tested in humans, the preceding results suggest a possible solution in aiding smoke cessation.



References
1.     Australian Government. (2010). AIHW. Risk Factors. [Viewed: 1.09.12]. Available: http://www.aihw.gov.au/risk-factors-health-priority-areas/
2.     Tabitha, M. (2004). PMC. Nicotine as Therapy. [Viewed: 2/09/12]. Available: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/
3.     Martin, T. (2011). About.com. Understanding Nicotine Addiction. [Viewed: 01.09.12]. Available: http://quitsmoking.about.com/od/nicotine/a/nicotineeffects.htm
4.     Australian Government. (2012). Australian Government. Quitting Methods. [Viewed: 3/09/12]. Available: http://www.quitnow.gov.au/internet/quitnow/publishing.nsf/Content/quitting-methods
5.     Reardon, S. (2012). NewScientist Health. Gene therapy curbs nicotine addiction in mice. [Viewed: 1.09.12]. Available: http://www.newscientist.com/article/dn21980-gene-therapy-curbs-nicotine-addiction-in-mice.html
6.     Autismspot. (2010). Autismspot. Lab mice. [Viewed: 6.09.12]. Available: http://www.autismspot.com/tags/Spot-Content-Tags/Lab-Mice

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