By Studying a Syndrome That Affects Only a Few, Scientists Hope to Help the Many Who Overeat

By Jennifer LaRue Huget
Tuesday, June 23, 2009

Imagine feeling hungry -- starving, even -- all the time, no matter how much you eat. So hungry that you would shoplift, sneak, steal or secretly order takeout food to sate your appetite, without regard for consequences.

Kate Kane doesn't have to imagine; she knows.

Washington Post readers met Kane in November 2004 when Ranit Mishori, a physician who frequently writes for the paper, reported on Kane's struggle with hyperphagia, or excessive eating. As Mishori noted, Kane's ravenous desire for food is a key symptom of Prader-Willi syndrome (PWS), a genetic disorder that affects not only appetite but also muscle tone, metabolism, stature and cognitive ability. About 4,500 Americans are known to have the syndrome, but experts believe it may be undiagnosed in as many as 25,000 others.

Kane's father, Jim Kane of Towson, this month helped organize a conference for researchers who work with genetic disorders that are characterized by hyperphagia. The event's prime goal was to have participants join forces to learn what causes hyperphagia, in hope of eventually devising a treatment or cure.

Those who gathered in Baltimore for the conference, including researchers from the National Institutes of Health, have another aim, though, one with far broader implications. If they can tease out the physiological, genetic and chemical causes of hyperphagia among people with disorders, that knowledge may prove a potent tool in combating obesity in the general population.

As Jim Kane puts it, "We study the extreme to learn about the general."

About five years ago, when 5-foot-5-inch Kate Kane was at her heaviest, she weighed 310 pounds. Today Kane, 27, lives in a group home in Wisconsin where access to food is severely restricted and where she receives support and counseling from dedicated aides. She consumes only 1,500 calories daily and is down to 160 pounds. She keeps busy at her two jobs, one assembling motorcycle-detailing kits and other such items for Harley-Davidson, another doing data entry. After work, she loves to play video games, and she's about to embark on an equestrian therapy program.

The young woman who once ordered food delivered to a nearby empty house -- because her family had alerted neighbors not to give her food and area restaurants not to honor her takeout requests -- is in a different mode now. She still feels hungry, she says, but not all the time. When asked how she's doing, Kane says she feels better about herself, in "better shape, healthier."

But while Kane's life has changed, efforts to understand and treat hyperphagia have progressed more slowly.

Five years ago, all eyes were on the hormone ghrelin, which is produced in the gut and which helps regulate hunger. People with PWS have dramatically higher levels of ghrelin than the general population, and researchers posited that reducing ghrelin would reduce appetite. Research hasn't borne that theory out yet.

But a study published last year suggested that ghrelin not only regulates hunger by stimulating the hypothalamus area of the brain but also affects parts of the brain responsible for pleasure and reward systems. That work both highlights the complex nature of hunger and opens new avenues for inquiry.

The lure of untangling the roots of obesity is drawing ever-increasing numbers of scientists to the field, says Tony Goldstone, a PWS researcher at Imperial College London, who attended the conference. Among the many questions to be explored through working with PWS as a model for obesity research: What role do sensory perceptions -- taste and smell -- play in hyperphagia? What do we learn from the fact that newborns with PWS actually eat too little, having apparently little or no hunger? How do brain chemistry and structure affect hunger? Is there an element of addiction in PWS and perhaps in other manifestations of obesity? Why do different people appear to receive different messages in their brains telling them when they're hungry or full? And might the genetic defect that appears to cause PWS have parallels in people who are otherwise healthy, perhaps giving them a genetic predisposition to overeating?

"The main message is that hunger and obesity are not just a matter of self-control," says Janalee Heinemann, director of research and medical affairs for the Prader-Willi Syndrome Association. "It's a pretty big, complex puzzle. Each system [of the body] plays into this and makes a difference, and each person is different."

As research inches slowly toward unraveling the mysteries of hyperphagia, Heinemann -- whose adult son has PWS -- keeps her eye on the plight of the obese. "If their problem is their metabolism, they may try and fail and then feel bad," she says.

"Unfortunately, nothing has really helped with their hunger. But if we accept that, okay, there are some people for whom it's not just a matter of self-control, we can try to intervene early. We can also get away from blaming the victim -- and the parents."

Administering growth hormones early on to kids with PWS can help, Heinemann reports, as those substances promote development of lean muscle mass, which in turn allows the body to burn more calories and thus stay thinner. But growth hormones are not a cure for PWS or for obesity.

Despite the efforts underway, those cures may be some time coming.

"In my more naive days, I thought we just needed to find the right pill," Heinemann says. Now, given what she's learned about the complex nature of both PWS and obesity, "I don't think there's going to be a pill."

Check out Tuesday's Checkup blog post, in which Jennifer discusses our perceptions of obese people. Subscribe to the Lean & Fit newsletter by going to and searching for "newsletters." And e-mail your thoughts to Jennifer at checkup@

© 2009 The Washington Post Company