Continued: Local firms hope to spark a solution for obesity

When it comes to battling obesity, is it better to

A. Push the body to do something?

B. Push the body to not do something?

Two Minnesota companies are trying to answer that question. EnteroMedics Inc. of Roseville has drawn considerable attention from investors and doctors for its promising VBLOC device, which uses electricity to block signals from the brain to the stomach, reducing the feeling of hunger. The company is now conducting a large-scale human trial and will seek approval from the Food and Drug Administration by the end of the year.

But another local start-up has been quietly working on its own treatment. Leptos Biomedical Inc. is developing a device to stimulate a nerve that controls how fast the body burns fat, or stored energy. The Fridley-based company recently raised $10 million from venture capital firms including Thomas, McNerney & Partners of Minneapolis and Technology Partners in Palo Alto, Calif.

"The most exciting aspect of this therapy is that it uses natural pathways to facilitate weight loss," said Leptos CEO Hans Neisz. "All that we are doing is enhancing those pathways and really lose weight with the help of the body instead of fighting the body.''

Experts caution that neuromodulation (also called neurostimulation) is still an emerging science and that manipulating the body's chemical-electrical nervous system can have unforeseen consequences. But the technique is effective in reducing pain and has shown promise in treating other diseases, including depression, urinary incontinence, migraines and epilepsy.

Earlier this month, the FDA approved a pacemaker-like device developed by Medtronic Inc. to treat obsessive compulsive disorder. Frost & Sullivan, a health care consultant, estimates the neuromodulation market, which totaled $642 million in 2007, could grow 16 percent a year until 2012.

Despite the steep downturn in health care venture investing in 2008, investment in neurodevices jumped 10 percent to $389 million, according to market research firm NeuroInsights.

In recent years, medical devicemakers and investors have turned their sights on obesity, a disease that affects about 70 million adults, or more than 30 percent of U.S. adults.

Karen Boezi, a San Francisco-based partner and co-founder of Thomas, McNerney who sits on Leptos' board of directors, said drugs designed to combat obesity have resulted in only minor weight loss. Drugs also cause side effects and take more time and money to develop.

Fighting obesity "is a huge unmet need," said Zack Lynch, publisher of Neurotech Insights, a newsletter. "It's a very important field of interest for venture capitalists. Because it is such a hot potential market, the companies are more secretive than you would expect."

IntraPace Inc. of Mountain View, Calif., and MetaCure USA Inc. of Orangeburg, N.Y., are both working on devices that control hunger by delivering electric pulses to the stomach.

Medtronic also is researching this area. In 2005, the company formed a new unit, Medtronic Obesity Management, after purchasing Transneuronix Inc., which focused on developing a pacemaker-like device to stimulate the stomach.

"Medtronic continues to explore effective therapies for patients who are obese," said spokesman Chuck Grothaus.

Am I full?

By stimulating only the stomach and intestines, those companies are missing half of the problem, Neisz of Leptos said. EnteroMedics and Leptos are the only two companies focusing on both the stomach and the brain, he said.

"The brain and the gut don't necessarily communicate very well," Neisz said. "The gut is telling the brain that I'm hungry; the brain receives those signals and sends food. The gut is somehow not sending back to the brain 'I'm full' or 'I've had enough.' It's really a disorder that is regulated in part by the brain, in part by the gut."

The body's autonomic nervous system controls bodily functions including digestion. The system has two types of nerves: parasympathetic and sympathetic. EnteroMedics' VBLOC device seeks to disrupt signals in the vagus nerve, a parasympathetic nerve that connects the brain to the stomach, intestines and pancreas.

Leptos' system targets one of the splanchnic nerves, a sympathetic nerve. Stimulating that nerve will activate the body's "fight-or-flight" system, a series of reactions to a perceived danger that include the burning of fat, accelerated release of energy and decreased feelings of hunger.

While quick to praise EnteroMedics, Neisz and Boezi suggest Leptos' approach might be safer and more effective than blocking nerve signals.

"We stimulate the nerve in a natural way," Boezi said. "Personally, I think there are potential advantages to the direct approach." But she cautions more data is needed. And EnteroMedics is several years ahead of Leptos, which is conducting a Phase II clinical trial.

In truth, manipulating any nerve signal can have unknown negative consequences, said Dr. Jaimie Henderson, an associate professor of neurosurgery at Stanford University School of Medicine and president of the North American Neuromodulation Society. He has no connection to either company.

"If the nerves perform a vital function, there can be health issues," said Henderson, who supports the emerging science. "Many nerves have multiple functions. By stimulating one nerve, you can have multiple effects. There are a lot of things we don't know about the nervous system."

EnteroMedics says clinical studies have proved the safety of its VBLOC system.

"Unlike neurostimulation approaches, EnteroMedics' neuroblocking therapy employs a mechanism of action which has been characterized, understood and defined," CEO Mark Knudson said in an e-mailed statement. "In clinical trials, this unique approach has resulted in significant excess weight loss ... and a positive safety record to date, including no deaths and no medically serious adverse events that are related to the device or therapy."

In any case, there's room for competition, Neisz said.

"This market is so large that 10 EnteroMedics and 10 Leptos Biomedicals can still make a very decent profit," he said.

Thomas Lee • 612-673-7744