Scientists ID Brain Area For Smoking Urge
Research Inspired By Stroke Victim Who Lost Urge To Smoke; Discovery Could Shed Light On Addiction

(AP) Damage to a coin-sized spot deep in the brain seems to wipe out the urge to smoke, a surprising discovery that may shed important new light on addiction.

The research was inspired by a stroke survivor who claimed he simply forgot his two-pack-a-day addiction — no cravings, no nicotine patches, not even a conscious desire to quit.

“The quitting is like a light switch that went off,” said Dr. Antoine Bechara of the University of Southern California, who scanned the brains of 69 smokers and ex-smokers to pinpoint the region involved. “This is very striking.”

The finding, reported in Friday's edition of the journal Science, points scientists toward new ways to develop anti-smoking aids by targeting this little-known brain region called the insula. And it sparked excitement among addiction specialists who expect the insula to play a key role in other addictions, too.

“It's a fantastic paper, it's a fantastic finding,” said Dr. Nora Volkow, director of the National Institute on Drug Abuse and a longtime investigator of the brain's addiction pathways.

“What this study shows unequivocally is the insula is a key structure in the brain for perceiving the urges to take the drug,” urges that are “the backbone of the addiction,” Volkow added.

Why? The insula appears to be where the brain turns physical reactions into feelings, such as feeling anxious when your heart speeds up. When those reactions are caused by a particular substance, the insula may act like sort of a headquarters for cravings.

Some 44 million Americans smoke, and the government says more than 400,000 a year die of smoking-related illnesses. Declines in smoking have slowed in recent years, making it unlikely that the nation will reach a public health goal of reducing the rate to 12 percent by 2010.

Nicotine is one of the most addictive substances known, and it is common for smokers to suffer repeated relapses when they try to quit.

So imagine Bechara's surprise at hearing a patient he code-named “Nathan” note nonchalantly that “my body forgot the urge to smoke” right after his stroke.

At the time, Bechara was at the University of Iowa studying the effects of certain types of brain damage after strokes or other injury. While Nathan was hospitalized, stroke specialists sent his information to that brain registry. He was 38, had smoked since 14, said he enjoyed it and had had no intention to quit. But his last puff was the night before his stroke. His surprised wife said he never even asked for a smoke while in the hospital.

It is not unusual for a health scare to prompt an attempt at quitting. “That's the quitting that's not as interesting,” Bechara said.

Instead, Nathan experienced what Bechara calls a “disruption of smoking addiction,” and he wanted to know why.

Bechara and colleagues culled their brain-damage registry for 69 patients who had smoked regularly before their injuries. Nineteen, including Nathan, had damage to the insula. Thirteen of the insula-damaged patients had quit smoking, with 12 of them quitting within a day of the brain injury and neither smoking nor even feeling the urge since then.

Of the remaining 50 patients with damage in other brain regions, 19 quit smoking but only four met the broken-addiction criteria.

If Bechara's findings are validated, they suggest that developing drugs that target the insula might help smokers quit. There are nicotine receptors in the insula, meaning it should be possible to create a nicotine-specific drug, Bechara said — albeit years from now.

More immediately, NIDA's Volkow wants to try a different experiment: Scientists can temporarily alter function of certain brain regions with pulses of magnetic energy, called “transcranial magnetic stimulation.” She wants to see if it is possible to focus such magnetic pulses on the insula, and thus verify its role.

Other neurologic functions are known to be involved with addiction, too, such as the brain's “reward” or pleasure pathways. The insula discovery does not contradict that work, but adds another layer to how addiction grips the brain, Bechara said.

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Brain Damage Sheds Light on Urge to Smoke
By Greg Miller
ScienceNOW Daily News
25 January 2007
Cigarette smokers who suffer damage to a particular brain region often lose the urge to smoke, according to a new study. Although brain damage is hardly a recommended treatment for smokers who want to quit, researchers say the findings provide important insight into the biological basis of addictive behaviors.

Previous research on addiction has implicated the insula, a brain region tucked into a deep fold in the cerebral cortex. In brain scans of cocaine addicts, for example, the insula lights up in response to images of drug paraphernalia. Those kinds of images also tend to give addicts an urge to take more drugs. Similarly, videos of people smoking stimulate the insula in smokers' brains. Such work suggests that the insula helps generate addicts' drug-related urges. So what would happen if the insula suddenly went offline?

Antoine Bechara, a neuroscientist at the University Southern California in Los Angeles, and colleagues investigated this question in 19 cigarette smokers who had suffered insula damage as a result of a stroke or other neurological problem. Twelve of these people stopped smoking immediately after their brain injury and reported feeling no urges to smoke and no relapses since they quit. "My body forgot the urge to smoke," one man told the researchers. Before his stroke he was smoking 40 unfiltered cigarettes a day and had no intention of quitting. Among a group of 50 smokers with brain damage that did not include the insula, only four quit the habit with comparable ease, the researchers report in tomorrow's issue of Science.

"This really helps us understand how the brain works in addictive disorders," says Edythe London, a neuropharmacologist at the University of California, Los Angeles. London says the new study bolsters the idea that the insula mediates emotional responses that contribute to addiction. "Gut feelings that are associated with cravings are probably only experienced after the information is processed in the insula," she says.

The findings could have implications for how to beat addiction, Bechara says. Based on the experiences related by the insula-damaged patients, he suspects that the insula is needed create the feeling that smoking is a bodily need. Bechara notes that other research has suggested that the bodily effects of smoking--particularly the effects on the airways--are a crucial part of the satisfaction smokers get from puffing away. If so, he speculates, smoking cessation therapies such as denicotinized cigarettes may ultimately prove more effective than nicotine patches because they provide physical sensations that stimulate the insula and satisfy the smoker.

Sanofi Says Acomplia Diet Pill Delayed a Third Time (Update8)

By Angela Cullen

Feb. 13 (Bloomberg) -- Sanofi-Aventis SA said its obesity pill Acomplia, the company's most important new product, was delayed in the U.S. for a third time and profit fell, hurt by copies of its Plavix blood thinner.

Net income dropped 4.2 percent to 1.38 billion euros ($1.79 billion), or 1.02 euros a share, in the fourth quarter from 1.44 billion euros, or 1.08 euros, a year earlier, the Paris-based company said today. Sanofi said late yesterday that U.S. regulators want another three months to review Acomplia.

The company needs the new diet pill because its top three products are being challenged by generic-drug makers. Profit from Plavix shrank in the quarter after cheaper copies entered the U.S. Sanofi lost a patent lawsuit last week on the Lovenox clot treatment and its exclusivity on the Ambien sleeping pill ends in April. Investors are worried by the delay to Acomplia, which analysts say may bring in more than $3 billion a year.

``It looks pretty bad on the generics front,'' said Romain Pasche, who manages about $800 million in drugs stock at Vontobel Asset Management. ``It's very important they come through on the pipeline. The delay to Acomplia isn't good news. There's uncertainty with the generics and nothing really moving on with their new drugs.''

France's largest drugmaker and Bristol-Myers Squibb Co., which markets Plavix in the U.S., are defending the medicine's patent in a New York court. Hanspeter Spek, who oversees Sanofi's drug unit, said Plavix copies by Apotex Inc. should be sold out by the end of the second quarter. Apotex sent out at least a six- month supply last year before a U.S. judge halted sales.

Shares Decline

The shares fell 1 euro, or 1.5 percent, to 66.80 euros at the close of trading in Paris. They've fallen 4.5 percent since the start of the year, trailing the 16-member Bloomberg Europe Pharmaceuticals index, which had gained 4.2 percent.

``2006 has been a difficult year,'' Spek said at a press conference in Paris. ``The market has changed, it has slimmed down in terms of growth.''

Sanofi was expected to earn 1.34 billion euros, or 1 euro a share, according to the median estimate of 10 analysts Bloomberg News surveyed by telephone and e-mail. Fourth-quarter sales rose 5.1 percent to 7.36 billion euros, the company said.

This year, Sanofi is targeting an increase in earnings per share similar to the 5.9 percent gain reported for 2006. Sanofi plans to increase the dividend payment by 15 percent to 1.75 euros a share for 2006.

`Questions'

``Sanofi really has to answer a huge number of questions, and I don't know that they've got the answers,'' Stephen Pope, head of equities at Cantor Fitzgerald Europe said in an interview. ``Profit is dropping. The delays to Acomplia in the U.S. are costing time and money and all the while the cash is draining.''

Chief Executive Officer Gerard le Fur, who took over from Chairman Jean-Francois Dehecq last month, presented the company's research progress today. Le Fur plans to submit 12 new drug applications for approval this year and next, or 18 including vaccines.

``We feel that our portfolio is probably not well known,'' Marc Cluzel, who heads the research and development unit, said at a briefing in Paris.

The company is working on drugs to treat depression and Alzheimer's disease as well as studies to expand the use of Eloxatin and Taxotere, its biggest cancer medicines. Sanofi also stopped developing a medicine for prostate cancer.

Acomplia Delay

Yesterday the company said the U.S. Food and Drug Administration will take until July 27 to complete analysis of human tests of Acomplia, the first in a new class of medicines to tackle obesity. Sanofi has submitted data showing the drug may also help patients with diabetes.

``Nobody has any doubts about its efficacy,'' Cluzel said about Acomplia. ``We hope to get FDA approval this year.'' He declined to comment on the reasons for the U.S. delay.

U.S. regulators first extended their review a year ago, saying the drug might be approved with the submission of more data. Sanofi completed its response last October and later said it didn't expect a decision until April.

Newspaper reports last month said Sanofi may bid for Bristol-Myers to gain new products and revive growth. The partners couldn't come to an agreement, the Times of London reported Feb. 10. Le Fur wouldn't comment on any discussions.

Sanofi would be interested in buying a biotechnology company as well as a transaction that would help boost its presence in Japan, Le Fur also said today.

Credit-default swaps based on 10 million euros of Sanofi bonds fell 0.4 percent to 14,754 euros today from 14,813 euros yesterday, according to data complied by Bloomberg. A decrease in price indicates improvement in the perception of credit quality, while an increase suggests deterioration.

Patent Disputes

Sanofi and Bristol-Myers suffered after Canada's Apotex sold copies for three weeks in August. Plavix sales rose 5 percent to 541 million euros after gaining 17 percent in the fourth quarter of 2005. Bristol-Myers sells the drug in the U.S. and Sanofi gets a share of the profit, so a drop in sales there affects the French company's earnings rather than revenue.

Last week, Sanofi lost a lawsuit over the patent of Lovenox, adding to its legal woes and increasing the pressure to get new drugs on the market. Today, Le Fur said the company will appeal the ruling and remained optimistic about the product.

Sanofi is also set to lose patent protection for Ambien, its third-largest drug, in April. It has already lost market exclusivity for cancer drug Eloxatin in Europe.

`Difficult Year'

``We can still expect a certain degree of generification'' this year, Chief Financial Officer Jean-Claude Leroy said. ``2007 will be a difficult year because of this phenomenon.''

Fourth-quarter sales were helped by a 30 percent increase in revenue from vaccines, where Sanofi is the market leader. The company in November won a contract from the U.S. government to supply a vaccine that may help protect against a pandemic of avian influenza. It plans to ship the vaccine this year.

To contact the reporter on this story: Angela Cullen in Frankfurt at acullen8@bloomberg.net

Last Updated: February 13, 2007 11:54 EST

The FDA is tough.
http://www.bloomberg.com/apps/news?pid=206...mp;refer=europe

My guess is that BigPharma wants to let Sanofi bleed a little bit more. Hey, bidness is bidness, right?

So what if the obese public is denied Acomplia?

Let 'em eat celery.

I don't get your logic. Can you explain?

Well, Sanofi stock is down. Ambien, their newest sleeping pill is going off patent, one of their other big bucks drugs, Plavix, is being litigated, and they would loooooove to have Acomplia for sale here in the USA.

But... there are AMERICAN Pharmas who would just as soon keep them OUT while they do their own r and d on fat pills.