Nicotine Noose

Published July 3rd, 2008

By Dale M. King and John Johnston
CITY EDITOR AND MANAGING EDITOR

It’s said that nicotine – and not the other chemicals – that makes cigarettes addictive.

But what is it about nicotine that hooks people to one of the most difficult habits to break?

Researchers at Florida Atlantic University are going to find out. And they have received an $820,000 “Team Science Program Grant” to do it.

“There is clearly a need for more systematic research of nicotine and other addictions at levels of analysis including genetic, biological, behavioral and social,” said Michael Friedland, M.D., dean of the Charles E. Schmidt College of Biomedical Science.

The funding comes from the Florida Department of Health and the James and Esther King Biomedical Research Program to study nicotine addiction.

“This is a highly competitive grant,” said Dr. Friedland, “and receiving this award is an important accomplishment for Florida Atlantic University.”

Looking at genetic and environmental factors, FAU researchers will work to understand the chemistry that underlies nicotine addiction, help to predict an individuals’ vulnerability to getting “hooked” -- and ultimately develop individual treatments to break the habit.

The team approach to this study is composed of three areas of research:

• Understanding the environmental and neurobiological mechanisms that are favorable for the expression or inhibition of pre-existing vulnerability to nicotine -- an important step for long-term success in nicotine abstinence, Friedland said.

• Examining the adverse effects of nicotine on the immune system to help forecast nicotine tumorigenesis with the objective of predicting adverse outcomes before a full pathology is observed. This, he said, could potentially reduce health costs related to diseases caused by cigarette smoking.

• Studying potential therapeutic targets that can reverse the predisposition to nicotine’s adverse effects in the immune system, providing an avenue for developing customized intervention strategies.  

Rodent Models

The research team led by Dr. Keith Brew, distinguished professor and Schmidt Senior Fellow, Dr. Ceylan Isgor, assistant professor, and Dr. Vijaya Iragavarapu, associate professor, in FAU’s Charles E. Schmidt College of Biomedical Science will investigate the novelty-seeking phenotype (vulnerability to psychostimulants) of a rodent model, selected either as a high or low level subject.

Researchers will examine the responses of certain aspects in the brain and immune system chemistry to combinations of nicotine and different types of stress that generate vulnerability to nicotine addiction.

“An individual’s tendency to become addicted to drugs, including nicotine, is determined by an interplay of genetic and environmental factors,” said Dr. Brew. “Novelty-seeking and sensation-seeking are concepts that are very useful in predicting human risk-taking behavior. Sensation-seeking behavior has a strong genetic element in humans that is mirrored in the rodent model of the novelty-seeking phenotype.”

Nicotine, a component of tobacco, is the primary reason that tobacco is addictive, although cigarette smoke contains many other dangerous chemicals, including tar, carbon monoxide, acetaldehyde, nitrosamines and others, the institute said.

“In order to quit smoking successfully for the long term, it is vital to understand the nature of nicotine addition,” said Isgor. “Even though individuals can initiate smoking cessation, there is as high as 70 percent relapse rate. This is why studying nicotine relapse is a top priority in tobacco research.” 

At the same time, Nabi Biopharmaceuticals is already developing NicVAX -- a vaccine to treat nicotine addiction and prevent smoking relapse. The vaccine is designed to stimulate the immune system to produce antibodies that bind to nicotine. A nicotine molecule attached to an antibody is too large to cross the blood-brain barrier. Therefore, NicVAX blocks nicotine from reaching its receptors in the brain and prevents the highly-addictive pleasure sensation experienced by smokers and users of nicotine products, Nabi says.

Progress Chart

In September 2005, Nabi announced that it received a $4.1 million grant from the National Institute on Drug Abuse (NIDA), which is part of the National Institutes of Health. NIDA has also funded, in part, the costs for toxicology testing and earlier clinical trials in the U.S. and contributed scientific and clinical expertise to the program overall.

In March 2006, Nabi announced that NicVAX® had received Fast Track Designation from the FDA, which facilitates the development of products that treat serious diseases where an unmet medical need exists. Nabi Biopharmaceuticals' intellectual property portfolio for technology related to NicVAX® includes both issued and pending patents in the US

And in 2007, test data from both six, nine and twelve month trial use of NicVAX revealed “statistically significant” cessation, and continued abstinence from nicotine use, NABI says.

NABI also said in 2007 that trials are expected to show that antibodies from NicVAX will last 12 months or longer.  If that proves to be true, it would support getting through the critical first year in which relapse ranges as high as 95 percent with other therapies.

According to the CDC, the 440,000 deaths in the U.S. attributable to cigarette smoking are equivalent to one-fifth of all U.S. deaths.

• More deaths are caused each year by tobacco use than by alcohol use, illegal drug use, suicides, motor vehicle accidents, murders and HIV combined
• Among nonsmokers in the US, approximately 3,000 lung cancer deaths and 35,000 coronary heart disease deaths occur each year as a result of exposure to secondhand smoke.
• According to the 2004 Surgeon General’s Report, nearly three quarters of smokers express a desire to quit and each year approximately 15 million smokers quit for at least a day, but fewer than 5 percent are able to stay tobacco-free for 3 to 12 months.
• Smoking harms nearly every organ of the body, causing many diseases and reducing the health of smokers in general.
• Quitting smoking has immediate as well as long-term benefits, reducing risk for diseases caused by smoking and improving health in general.