One of the biggest challenges for people living with Prader-Willi syndrome (PWS) is hyperphagia, the overwhelming drive to eat. For many years, researchers believed this was because the body wasn’t producing the hormones that tell us we’re full. However, recent research has revealed something surprising.
Scientists have found that people with PWS produce normal levels of a hormone called CCK (cholecystokinin) after eating. CCK is one of the body’s natural “I’m full” signals, released during and after a meal. In most people, this hormone sends a message to the brain that it’s time to stop eating. But in PWS, that message doesn’t appear to have the same effect.
So, if the signal is there, why isn’t it working?
Researchers believe the problem may not lie with the hormone itself, but with the way the brain processes the message. In simple terms, the brain may not be properly “hearing” or responding to the signal telling it that enough food has been eaten
To investigate this, Dr. Haijiang Cai and his team at the University of Arizona are studying how the brain responds to fullness signals in PWS. Their research focuses on a gene called MAGEL2, which is thought to play an important role in appetite regulation and is affected in many people with PWS.
Using a mouse model that shares some of the same appetite-related difficulties seen in PWS, the researchers discovered that even when additional CCK is given, food intake is not reduced. This mirrors what has been observed in people with PWS and suggests that the brain pathways responsible for recognising fullness may not be functioning as expected.
The project aims to identify exactly which parts of the brain are failing to respond to these signals and whether they can be stimulated in other ways. If successful, this work could help scientists identify new treatment targets for hyperphagia.
While this research is still at an early stage, it represents an important shift in thinking. Rather than asking whether the body is producing the right signals, researchers are now trying to understand how the brain receives and interprets those signals.
Ultimately, this could lead to new treatments designed to help the brain recognise natural feelings of fullness and improve appetite regulation for people with PWS