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Tuesday, September 19, 2006

The Future of Weight Loss

By L.C. Smith

Conventional wisdom says that staying thin is simply a matter of willpower and sweat. But science suggests that the key to being in shape is a bit more complicated. Even if you eat right and stay active, obesity may be an inevitable part of your life -- especially if you were unlucky enough to have inherited a genetic predisposition for the condition. Call it the "beer-belly gene."

But whether you're chubby because you have bad hand-me-down DNA, a time-consuming job that doesn't allow you the luxury of working out, or simply because you can't stand the thought of life without fudge, your fortunes -- and your waistline -- could soon be a-changing.

Yes, exercise and diet are still very important in the war on weight, but within a few years it could be a handful of pills or quick voluntary surgery that will be doing the heavy lifting.

Although doctors have been looking for a miracle weight loss pill for decades, the quest picked up serious steam about 10 years ago, when a scientist at New York City's Rockefeller University discovered leptin, a hormone that controls the body's storage of fat. Combine that knowledge with more recent findings on how metabolism works and how fat cells get their nutrients, and it's no longer a matter of if a fat-fighting pill can be developed, but simply a matter of when it will be ready for devouring.

Experts, however, remain divided on just how effective any pill could be. "I hate to be pessimistic," sighs Manfred Kroger, Ph.D., professor emeritus of food science at Penn State, "but I've been a nutritionist for a long time, and I've seen a lot of different weight-loss treatments come and go. The bottom line with all the ones that sort of worked in the past is that they also encouraged the people who were using them to eat less and work out more. If we can do that, we don't need a pill."

Still, there are many in the nutrition world who would welcome other options besides the tried and true "calories in, calories out" formula.

"Not every method of weight loss works with every person," says Kathleen Zelman, R.D., director of nutrition for WebMD.com's Weight Loss Clinic. "The more tools we have for weight loss -- whether they're drugs, medical treatments, or educational programs -- the better off we're all going to be, and I do think there are some options on the horizon that hold great promise.

"Regardless of whether they really want to change the planet or are just cashing in on a trend, international drug and medical-technology companies are scrambling to get their weight-loss products on the market as quickly as possible, and are pouring millions of dollars into research and development in the process.

And the early prognosis for their efforts is very good, with some medications already appearing to be more effective than anything currently in your neighborhood pharmacy. Existing weight-loss drugs, such as Xenical, for example, only help most people shed an average of 10 pounds -- not nearly enough to help an obese man once again see his feet. The next generation of drugs and medical treatments promises to put those numbers to shame. Here's a preview of five up-and-coming fat fighters we think hold the most promise for helping America slim down.

Rimonabant
The skinny: Paris-based Sanofi-Synthelabo is developing a potentially wicked one-two punch in the fight against flab. Unlike most weight-loss drugs under development (which tend to target either the brain or the gut), rimonabant performs its magic in both areas, helping to eliminate hunger and promote feelings of fullness at the same time.

According to Jean-Pierre Despres, Ph.D., of Laval University in Quebec, the drug works by blocking cells in the brain that, when stimulated by signals from the stomach, cause you to feel sensations of hunger. In its most recent human trial, researchers found that overweight men and women who took rimonabant for a year dropped nearly 20 pounds. Subjects ate less because they felt full sooner.

They were also able to lower their triglyceride levels by 15% and raise levels of HDL, the so-called "good" cholesterol, by 22%, two changes that help seriously reduce a person's risk of heart disease. Better still, the drugs seem custom designed for overweight men, since most of the weight that patients lost came from around their middle.

That's an important distinction and benefit, because unlike women, who generally accumulate fat in their thighs and hips, obese men store the majority of their dangerous and most deadly fat in the belly.

Time to market: About two years, should the clinical trials currently underway prove successful.

Axokine
The skinny: The discovery of leptin, a protein produced by fat cells that signals the brain to stop eating, was supposed to lead to a breakthrough weight-loss drug. Then we learned that obese folks are resistant to the stuff. Now scientists at Regeneron, based in New York state, are experimenting with a protein that acts on the same feeding center within the brain as leptin does.

The drug, called Axokine, quells the urge to eat by convincing the brain that all the fat cells within the body are full and don't need any additional nutrients. Although Axokine doesn't work for everyone, 15% of individuals who took the medication for at least a year responded particularly well, losing an average of 34 pounds. "This led us to suspect that the drug may work better on people with certain genes and genetic types than it does on others," says George Yancopoulos, M.D., Ph.D., Regen- eron's chief scientific officer and president of its laboratories. Now the company just needs to figure out who those folks are exactly, he says.

Time to market: Within 10 years.

Gastric Pacer
The skinny: It says something about the arduous battle of the bulge that the only surefire cure for obesity now available isn't even a drug at all. Instead, it's a drastic surgery called gastric bypass, which reduces the stomach to the size of a Ping-Pong ball. Although the procedure is gaining in popularity -- more than 100,000 obese people underwent gastric bypass last year -- it still carries serious risk of heart attack, respiratory failure, and even death.

But an alternative may soon arrive in the form of a gastric pacer. Designed by an Italian doctor in the 1990s, the pacer is a battery-powered device the size of a cigarette lighter that's surgically implanted under the skin of the abdomen. The pacer regularly sends a pulse to the stomach through two wires, giving people the sense that they're "full" sooner than usual. (The wires are placed outside the stomach, so you aren't served an electric shock with your meal.)

In the most recent study of the gastric pacer's effectiveness, obese people who were outfitted with the device for a year lost, on average, 18% of their total body weight. Although that's still well below what they would lose with gastric-bypass surgery, which generally cuts away at least two-thirds of excess body weight, experts believe the pacer could become a viable option for high-risk patients or people worried about the harmful effects of the more severe gastric bypass.

Time to market: A 200-patient trial of the pacer is underway. FDA approval hinges on these results.

PYY
The skinny: In the mid-'90s, two London scientists at Hammersmith Hospital uncovered a protein produced in the intestine that can suppress appetite. The only problem, they later found, is that overweight people make about a third less of the protein -- called peptide YY3-36 (PYY) -- than thinner people. Bump up PYY levels in the overweight, the researchers theorized, and you may cure the root of their obesity. One possible way to do just that: a nasal spray that would juice people up with PYY before they chow down. More protein can lead to weight loss.

Cut to 2004, and a Washington state-based company called Nastech Pharmaceutical has developed just such a spray, containing PYY and capable of boosting levels of the protein in the bodies of people who take a sniff. Although still in preliminary trials, the spray has already had great success -- helping one group of overweight men and women, for example, cut their calorie consumption by at least 15%. Real-world translation: A whiff like that could help you lose six or more pounds a month. "If the product is as safe as we think it is," says Nastech CEO Steven C. Quay, M.D., Ph.D., noting that the only side effect is mild nausea, "it could be used by people who are obese or just slightly overweight."

Time to market: Nastech is currently prepping the spray for human trials. Quay believes it could be approved within three to four years' time.

Fat Blasters
The skinny: In the late '90s, a group of scientists at M.D. Anderson Cancer Center in Houston learned how to fight cancer in mice by killing the blood vessels that feed the animal's tumors. Then the researchers turned their attention to fat cells, hoping to replicate the finding -- something they finally achieved last spring. But in one of the most radical approaches to fighting fat, the researchers didn't just learn to shrink cells, they actually found a way to make them self-destruct, cutting off the flow of blood to cells and effectively starving them to death.

In the researchers' most recent study, plumped-up mice were injected with a substance, called synthetic peptide. Within weeks, the mice had reverted to normal mouse size, shedding about 30% of their total body weight. Better still, the animals' elevated blood-sugar and cholesterol levels, which had risen dangerously high, also dropped back to normal.

Mikhail Kolonin, Ph.D., one of the study's researchers, believes the therapy could eventually be used as the prototype for a human drug, but "we need to do more studies," he says. "We didn't follow up to see if the mice might lose too much fat over time, which could be lethal -- even in severely overweight people."

Time to market: Unknown. A trial of the drug in overweight baboons is set to begin this month. Even if that works, Kolonin says, it could be years before the treatment makes its way to human experiments.

1 comment:

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