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Gene therapy 'immunisation' against nicotine successful in mice

2 July 2012
Appeared in BioNews 663

A gene that codes for nicotine antibodies has been successful in immunising mice against the drug's effects. But although the treatment appears to work in mice, any 'smoking vaccine' is still a long way off.

The therapy, created by Ronald Crystal, professor of Genetic Medicine at Weill Cornell Medical College in New York, differs from previously attempted vaccines in its unconventional, gene-based approach.

The gene in question is placed into a carrier called an adeno-associated virus (AAV) together with information that directs the virus towards hepatocytes, or liver cells. Once it reaches the hepatocytes, the gene is inserted and the cells produce a continuous supply of nicotine antibodies.

After the researchers injected the 'vaccine' into nicotine-addicted mice, the animals started to circulate the antibodies in their bloodstream. To test whether these antibodies were doing the job they were designed for, the research team then injected the mice with two cigarettes worth of nicotine. The antibodies managed to capture 83 percent of nicotine before it reached the brain.

The behaviour of the mice changed as well: whereas mice usually reacted to nicotine by 'chilling out', as Professor Crystal put it, the nicotine-addicted mice treated with gene therapy retained a normal activity level.

The therapy is meant to target the addictive effects of nicotine. With nicotine removed from the bloodstream and unable to reach the brain, cigarettes would no longer give the pleasure they used to - making it easier to give up the habit of smoking.

'As far as we can see, the best way to treat chronic nicotine addiction from smoking is to have these Pacman-like antibodies on patrol, clearing the blood as needed before nicotine can have any biological effect', Professor Crystal said.

However, it is uncertain how long it would be until the gene therapy could be tested in humans. So far, AAV-based gene therapy has only been clinically tested in people with HIV (human immunodeficiency virus) or terminal cancer, as the potential benefits more clearly outweigh the risks in these cases.

Unlike patients with terminal diseases, 'smokers are normal people with decades of life ahead of them', Thomas Kosten, professor of Psychiatry and Neurology at Baylor College of Medicine in Houston told New Scientist. Professor Kosten believes that a better, safer vaccine will be developed by the time AAV-gene therapy has passed the necessary safety tests.

Therapies to help people quit smoking are highly sought after; as many as 70 to 80 percent of people who attempt to quit smoking relapse within half a year. Previous attempts to create a nicotine vaccine failed in clinical trials. These vaccines consisted of nicotine antibodies, and had to be injected repeatedly, making the treatment expensive.

AAV-Directed Persistent Expression of a Gene Encoding Anti-Nicotine Antibody for Smoking Cessation
Science Translational Medicine |  27 June 2012
A jab to quit smoking: 'DNA vaccine' will halt nicotine cravings and could even be used to stop children starting the habit
Mail Online |  28 June 2012
Gene therapy curbs nicotine addiction in mice
New Scientist |  27 June 2012
New Vaccine for Nicotine Addiction
Science Daily (press release) |  27 June 2012
'Smoking vaccine' blocks nicotine in mice brains
BBC News |  27 June 2012
Vaccine to help smokers quit is a long way off
NHS Choices |  28 June 2012
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