A chemist in Syracuse University’s College of Arts and Sciences has been awarded a major grant extension, enabling him to continue studying a rare genetic disorder known as Prader-Willi Syndrome (PWS).
James Hougland, assistant professor of chemistry, has received an additional $76,000 from the Foundation for Prader-Willi Research to build on his previous study of insatiable hunger associated with PWS. He plans to use the extension to investigate biochemical signaling in hunger, in hopes of finding a treatment for PWS.
Hougland says that people afflicted with PWS know all too well the intense desire to eat, independent of how much food they consume. “You know what it’s like to have an itch in the middle of your back that you can’t scratch?” he asks. “Imagine that’s hunger. Even if they eat enough, PWS patients still feel hungry.”
Insatiable hunger in PWS is of particular concern to Hougland because it can lead to morbid obesity. In fact, cardiovascular conditions resulting from obesity have been a source of PWS-associated mortality.
The Hougland Lab focuses on the biochemical pathway underlying hunger signaling. Much of their work involves the “hunger hormone” ghrelin, which is produced by cells in the gastrointestinal tract. Ghrelin then enters the bloodstream and is transported to the hypothalamus in the brain, where it signals hunger. Only when one eats do ghrelin levels drop, thus turning off the impulse to consume more.
With PWS, insatiable hunger results when ghrelin signaling has gone awry: Levels remain high and don’t cycle down, after eating. One way to tackle this problem, Hougland says, is to stop the manufacture of the mature ghrelin protein.
This is done with an enzyme called ghrelin O-acyltransferase (GOAT). Before ghrelin can tell the brain it is hungry, GOAT tacks on a fatty acid chain to the signaling molecule. Hougland is using his grant award, as well as its extension, to figure out how to inhibit GOAT from adding this fatty acid.
“Because PWS is a genetic syndrome, you can’t cure it, but you can certainly treat the symptoms,” he says. “Even if PWS patients are overproducing ghrelin, we can try to block the enzyme that activates ghrelin. This will cause them to pump out an inactive form of it to blunt the hunger signal.”