Gene therapy 'immunisation' against nicotine successful in mice

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.