-- [ From: Bob Martone * EMC.Ver #2.5.3 ] -- Possibly a new thread in our search for a cure? Could this mean that a CYP2A6 gene defect could have a neuro protective role in preventing Parkinson's Disease. Dr. Langston last week in Washington said all 34 PD studies of smokers versus non smokers have confirmed that smokers are less likely to get PD. Bob Martone(Nancy53/23) -------- REPLY, Original message follows -------- Date: Wednesday, 24-Jun-98 05:18 PM From: Judith Richards \ Internet: ([log in to unmask]) To: Parkinsn List Mail \ Internet: ([log in to unmask] utoronto.ca) Subject: non PD, but further to the smoking thread... 06/24/98 Gene defect is why some people never become smokers By Patricia Reaney LONDON, June 24 (Reuters) - Scientists have discovered why some people never get addicted to cigarettes and why all smokers do not develop tobacco-related cancers. For some people, a common genetic defect reduces their ability to metabolise nicotine, the addictive ingredient in cigarettes, making them less likely to become smokers. If they do take up the habit, they will smoke fewer cigarettes. In a letter in the scientific journal Nature on Wednesday, researchers from the University of Toronto said smokers with a faulty CYP2A6 gene also have increased protection against cancers because their bodies are less efficient in turning the dangerous ingredients in cigarettes into carcinogens that produce cancer. ``This is the first gene that has clearly been identified that affects the development of the regular smoking pattern,'' Dr Rachel Tyndale, a pharmacologist at the university, said in a telephone interview. The CYP2A6 gene produces an enzyme that metabolises nicotine . If scientists could block the function of the enzyme with a drug they may be able to prevent and treat people addicted to tobacco. ``We're interested therapeutically because we believe we can imitate the genetic defect and use this as a (drug) therapy,'' said Tyndale. People addicted to cigarettes must adjust their smoking to maintain constant blood and brain nicotine levels. A drug that could block the metabolism of nicotine could prevent people from becoming addicted to tobacco or could help smokers maintain their nicotine level for much longer so they would need fewer cigarettes, making it easier for them to eventually quit. Tyndale envisions the development of a pill that smokers could take in the morning that would block the enzyme function for upwards of 24 hours. The researchers are testing how smoking behaviour can be changed in humans. The next step would involve a pharmaceutical company to commercialise any treatment. Tyndale said if all goes well a drug therapy could be just a few years away. Further down the road the gene could be a target for gene therapy. The medical implications of an effective treatment to prevent smoking are enormous. Approximately one-third of the world's population smokes, despite the link with lung cancer and respiratory and heart diseases. Studies have shown that up to 80 percent of smokers acquire the habit by the time they are 15 or 16 years old. There are three types of CYP2A6 genes, one normal and two defective. Everyone has two of the genes, one inherited from each parent. One percent of the population carry two deficient CYP2A6 genes, which gives them the most protection from tobacco. People who have one functioning and one faulty gene also have the defect. Tyndale and her colleagues, Edward Sellers and Michael Pianezza, studied 184 people who had never smoked and 244 people who were addicted. They said 20 percent of non-smokers carry a defective version of the gene, compared to only 10 percent of smokers. Among the smokers, those with the faulty gene smoked an average of 129 cigarettes a week compared to 159 a week for people without the defect. ``Even just having one half of the impairment can make a big difference in terms of whether people are likely to become smokers. If we can imitate that, or imitate the people who have no nicotine metabolism, we feel that this would be a really strong therapeutic approach,'' said Tyndale. ^REUTERS@ -- Judith Richards, London, Ontario, Canada [log in to unmask] -------- REPLY, End of original message -------- -- Bob Martone(Nancy 53/23)