28 April 2005— All over the industrialized world people are getting fatter. Obesity rates in the United States, for example, have ballooned from about 10 percent in the early 1960s to 30 percent in 2000. And with obesity come a cohort of other health problems including diabetes, heart disease, and stroke. Though a recent epidemiological study has cast doubt on how deadly obesity really is—revising the number it kills each year in the United States downward from 400 000 to 112 000—the risk is still enough to drive more than 100 000 obese people per year to seek a surgical solution. Gastric bypass surgery is a radical remodeling of the gut that reduces the stomach's volume and scales back a person's ability to absorb nutrients. But the surgery comes with a risk of complications—including death—and it is irreversible. So a group of companies have set about adapting that old standby of the medical device industry, the pacemaker, to mimic the effects of gastric bypass surgery—but reversibly, and with minimal surgery or, in one case, none.
The concept attracted over US $40 million in venture capital last year, and progress has been rapid. One firm's device is approved for use in the European Union and Canada, and the company, Transneuronix Inc., in Mt. Arlington, N.J., recently finished enrolling hundreds of patients in the trials it will use to gain approval in the United States. The other companies plan trials in humans starting this year.
The Transneuronix device is a pocket-watch-size stimulator that is implanted beneath the skin of the abdomen. Electrodes lead from the stimulator to the stomach wall and deliver 4 to 12 bursts per minute of 2- to 100-hertz pulses. The stimulator settings are adjusted with a short-range wireless link similar to those used to program pacemakers. In the last nine years, more than 700 people have received the gastric stimulator, and two years following the implantation on average they had lost and maintained the loss of 35 percent of their excess weight—about half of what gastric bypass surgery delivers. So far, no one has died from the Transneuronix implant, and there have been no major complications.
Representatives of Transneuronix would not comment for this article, but according to published clinical studies, patients with the device find it easier to become sated and so do not eat as much. The electric pulses are thought to disrupt the grinding motion of the stomach, thus slowing digestion. In addition, recent studies show that the stimulation alters the release of certain hormones in such a way that a person would feel full for a longer time.
This company clearly has the edge over its competitors, but they will all soon start human trials, and some are riding Transneuronix's clinical coattails. Intrapace Inc., in Menlo Park, Calif., for one, is developing a pacemaker that works in an almost identical fashion. The only difference is that instead of having the device surgically implanted, the patient, in effect, swallows it. "One thing that was very obvious to us: the stomach has wonderful access through the mouth," says Intrapace CEO Mir Imran. The stimulator is pushed down the throat using an endoscope and stitched to the inside of the stomach wall. The electrode lead is then fixed to the other side of the stomach. "Obesity therapy is an elective procedure," notes Imran. "I firmly believe that patients would be more attracted to simple outpatient endoscopic procedures."
Intrapace had to rethink the pacemaker a bit for a journey down the throat and a home inside the stomach. "We really can't put a flat, hockey-puck-shaped device down someone's throat," says Imran. So the stimulator was engineered into a package about the size and shape of a AA battery. The implant and its electrode leads also required new materials to survive in the stomach's acidic environment.
EnteroMedics Inc., in St. Paul, Minn. takes a different approach: rather than stimulating the stomach wall, its stimulator blocks traffic on the nerves that penetrate the stomach. The device sends biphasic electrical signals to the trunks of the vagus nerve just as it enters the stomach. The signal forces the nerve's cells into a state in which they cannot transmit information either up from the stomach or down from the brain. These signals are crucial to everything about eating.
Ordinarily, when you begin a meal the brain tells the stomach to slacken so it can accept more food. But with the vagus nerve blocked, the signal never gets through, and "you can't eat as much in one sitting," says Mark Knudson, EnteroMedics CEO. The blockage also slows the stomach's grinding motion, keeping food in the stomach longer, and it suppresses the release of digestive enzymes. With fewer digestive enzymes, less of the food that does get eaten is absorbed. And finally, blocking the vagus should mean no hunger pangs, as much of the information about satiety travels along this nerve.
Though EnteroMedics has yet to do its first patient testing, on 30 March it scored a partnership to develop the device with one of the premier medical centers in the world, the Mayo Clinic in Rochester, Minn.
Another electronic implant hopeful is Metacure Ltd., in Tirat Carmel, a spinoff of Impulse Dynamics Israel Ltd., which makes stimulators to treat heart failure. Company executives refused an interview, but a spokesperson said that Metacure is beginning trials in humans. The obesity device is based on the electrical stimulation technology that Impulse Dynamics uses to increase the ability of heart muscle to contract. For a matter of milliseconds immediately following a heartbeat, the muscle is immune to attempts to electrically trigger another beat. However, if a biphasic pulse of current is applied to the muscle during that time, calcium ions flow into its cells and the amount it contracts increases. Metacure plans to use similar stimulation in the stomach, though the company would not specify how this would lead to weight loss.
Electrical stimulators aren't the only alternative to gastric bypass surgery. Laproscopic banding, pinching off part of the stomach with an inflatable plastic tube, has been in use for several years. But it merely makes the stomach smaller, leaving the absorption of food unchanged. It also comes with its own set of complications and leads to less weight loss than bypass surgery. Other nonelectrical devices are in the works. Start-up GI Dynamics Inc., in Watertown, Mass., is developing one such device, though the company will not describe it beyond confirming that it does not rely on electrical stimulation.
If and when these devices go on the market they will compete with surgery, each other, and drugs. Enteromedics' Knudson thinks devices may have the edge over drugs, at least. He notes that control of the gut is very complex, involving as many as 25 different neurochemical signals. A drug can typically act on only one. "To find a magic pharmaceutical bullet is way off in the future, if it will happen at all," he says.
And not all the devices may wind up in direct competition. "There will ultimately be many different types of patient populations and market niches," says GI Dynamics' CEO Stuart A. Randle, adding that certain "new therapies will work better in some than in others." At this early stage, however, he says, no one knows who those populations are.
While the rush to find electronic analogues of bypass surgery has drawn a great deal of attention and private funds, U.S. government scientists are trying to get engineers to work on devices that can help keep people from becoming obese in the first place.
At the core, weight problems are an imbalance between how much you eat and how many calories you burn each day. Abby G. Ershow, the nutrition program officer at the National Heart Lung and Blood Institute in Bethesda, Md., describes what is needed as "a magic wristwatch" that can tell you when your caloric intake is out of balance with your burn rate. "The trick is having something that genuinely works, is easy to use, and can be translated into how people can change their behavior," says Ershow. Nothing like that exists today, but Ershow is hoping some small business research grants funded by the National Institutes of Health will help technology move in that direction.