Thursday, May 15, 2008

A New Way to Treat Obesity

Researchers believe that they might be able to combat obesity by blocking a nerve that helps regulate digestion.

Stomach signals: In VBLOC therapy, two electrodes are surgically implanted at the top of the stomach to block signals from the vagus nerve. In the illustration above, green arrows indicate neural signals traveling from the brain to the digestive system, while blue arrows indicate signals traveling from the stomach and intestines to the brain. A small regulator (shown at right) that controls the frequency and amplitude of electrical signals is implanted beneath the skin and connected to the electrodes (shown here in gray) via wires. The electrical signals can be changed at the physician’s office via a wireless controller. The device is currently being tested in clinical trials and has not yet been approved by the FDA.
Credit: Enteromedics

An implantable device that uses electrical signals to block the vagus nerve, which helps regulate digestion, has shown early success in clinical trials. The experimental therapy, developed by Enteromedics, a medical-device company based in St. Paul, MN, is part of a growing trend to develop alternatives to gastric bypass surgery, an often highly successful but invasive procedure to curb obesity.

"We need an approach to this that is safer than current alternatives and efficient to perform," says Christopher Thompson, a surgeon at Brigham and Women's Hospital who tests new surgical tools and methods.

As the obesity epidemic booms, so has the number of people undergoing gastric bypass surgery, a procedure in which the stomach is surgically reduced to about the size of a lemon. The American Society for Metabolic and Bariatric Surgery estimates that gastric bypass rates have doubled in the United States in the past five years, from about 100,000 in 2003 to approximately 200,000 in 2007.

While gastric bypass often leads to dramatic weight loss, only a small percentage of people eligible for the surgery--those with a body mass index (BMI) of more than 35--actually choose to do it. That may be because the procedure comes with some serious risks and is irreversible, requiring permanent dietary restrictions and nutritional supplements. "Many people who really need the procedure don't seek out medical attention because they're worried about potential medical complications," says Thompson. "We're only treating a small fraction of eligible patients."

A new option is on the horizon. At a neurotechnology conference in Boston last week, Enteromedics described positive preliminary results from a European trial of its vagal blocking therapy, called VBLOC.

The device uses an electrical stimulator to block signals from the vagus nerve, which connects the brain to the gastrointestinal organs, regulating hormones and other factors involved in satiety and hunger. "It controls how the stomach expands when we start to eat," says Mark Knudson, chief executive officer at Enteromedics. "If it doesn't expand, we become full after a few bites."

In the procedure, two small electrodes are laparoscopically implanted next to vagal nerve fibers at the top of the stomach. A regulator implanted under the skin sends high-frequency pulses of electricity to the electrodes, which are thought to block the signals coming from the vagus nerve. While scientists don't know exactly how it works, they theorize that the device blocks signals that would normally tell the stomach to expand to accept food, as well as trigger the release of digestive enzymes and gastric acid, potentially slowing digestion. Many patients report feeling less hungry and feeling fuller earlier, says Knudson.

An analysis of nine patients who were among the first to receive the implant shows that they lost almost 30 percent of their excess body weight after nine months. And preliminary data from a larger group indicates that following the procedure, patients ate an average of 500 fewer calories per day. "That's less than you'd see for a lap band or a gastric bypass, but it's still pretty good," says Janey Pratt, a surgeon at Massachusetts General Hospital, in Boston.

Enteromedics is now enrolling patients for a larger, placebo-controlled trial of 300 patients in the United States and Australia. Two-thirds of the participants will have the device turned on immediately following implantation, while it will remain off in the other third for several months. Scientists will compare weight loss and other factors, and follow all patients for four years to assess long-term effects.

"I'm not sure it will ever have the same weight loss as gastric bypass would have," says Noel Williams, director of the Bariatric Surgery Program at the University of Pennsylvania School of Medicine, in Philadelphia, who is not involved in the trials. "But a certain population of patients, those with BMIs that are not as high [as candidates for gastric bypass], might do well with it."

Proof of principle for the vagus nerve as a target for obesity came accidently. In the 1950s, surgeons often severed all or part of the nerve as a treatment for ulcers. (The vagus nerve also controls the release of gastric juices.) Many people who underwent the procedure reported feeling less hungry and lost weight. But the effect was short lived: after two or three months, the body adjusted, and patients returned to their old eating habits. Knudson and his team believe that intermittently blocking the nerve can prevent the nervous system and digestive organs from compensating for the change.

Experts warn that testing of this device is still in the early stages. It is just one of dozens of medical devices being developed to target the gastrointestinal system in obese patients, including new versions of lap bands, devices that take up space in the duodenum, and devices that alter gastric motility, says Lee Kaplan, director of the weight center at Massachusetts General Hospital. In fact, some devices that stimulate rather than block the vagus nerve are also under development, although they're in an earlier stage of research. "At this point, no one can say with any certainty which device is most likely to be successful," says Kaplan.

Previous efforts to use electrical stimulation to treat obesity have had mixed results. A device that targeted electrical stimulation directly to the stomach helped some people but not others. "The problem was that research was never done to figure out what was the mechanism of action," says Scott Shikora, chief of bariatric and minimally invasive surgery at Tufts Medical Center, in Boston. Shikora, who is overseeing one arm of Enteromedics' new trial, says that he is optimistic about the new device.

One of the problems with electrical stimulation therapies is in determining the type of electrical signals to use. Knudson says that VBLOC therapy gets around this problem by using high-frequency signals to completely block the nerve. However, it's not yet clear what the broad impact will be. So far, more than 100 patients have undergone the procedure, and no deaths or serious adverse events linked to the device have been reported. But the company says that data on milder side effects has not yet been reported.