Gene Therapy Cures Nicotine Addiction in Mouse Model

A novel gene-therapy approach has been used to treat nicotine addiction in a mouse model that mimics chronic cigarette smoking in humans.

Addiction to the nicotine in cigarette smoke prevents many smokers from quitting. To overcome this addiction investigators at Weill Cornell Medical College (New York, NY, USA) developed a genetics-based vaccine. They incorporated the gene for an antinicotine monoclonal antibody into an adeno-associated virus (AAV). The vector, which expressed the gene for a full-length, high-affinity, antinicotine antibody derived from the Fab fragment of the antinicotine monoclonal antibody NIC9D9 was designed to infect liver cells and then manufacture the antibody.

The vector was administered to a population of laboratory mice. Results published in the June 27, 2012, online edition of the journal Science Translational Medicine revealed that in the treated mice blood concentrations of the antinicotine antibody were dose-dependent, and the antibody showed high specificity and affinity for nicotine. The antibody shielded the brain from systemically administered nicotine, reducing brain nicotine concentrations to 15% of those in control mice. The amount of nicotine sequestered in the serum of vector-treated mice was more than seven times greater than that in untreated mice, with 83% of serum nicotine bound to immunoglobulin G. Treatment with the vector blocked nicotine-mediated alterations in arterial blood pressure, heart rate, and locomotor activity.

"Our vaccine allows the body to make its own monoclonal antibodies against nicotine, and in that way, develop a workable immunity," said senior author Dr. Ronald G. Crystal, professor of genetic medicine at Weill Cornell Medical College." 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."

"While we have only tested mice to date, we are very hopeful that this kind of vaccine strategy can finally help the millions of smokers who have tried to stop, exhausting all the methods on the market today, but find their nicotine addiction to be strong enough to overcome these current approaches," said Dr. Crystal. "Smoking affects a huge number of people worldwide, and there are many people who would like to quit, but need effective help. This novel vaccine may offer a much-needed solution."

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