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We provide you with articles on brain science, timely topics, and healthy living for those affected by neurologic challenges or seeking better brain health.  

By ABBY ELLIN

Drugs in the Pipeline for Prader-Willi Syndrome

In the October/November 2018 issue, we profile Mayim Bialik, who plays Dr. Amy Farrah Fowler on The Big Bang Theory, and her quest to interest more girls in science. We also mention her doctoral thesis on obsessive-compulsive disorder in people with Prader-Willi syndrome, a rare genetic disorder characterized by an insatiable hunger that leads to compulsive eating and obesity. In this online exclusive, we look at drugs in development and promising research in the pipeline.

At least five drugs designed to help with the insatiable hunger of Prader-Willi syndrome are being tested in clinical trials, says Shawn McCandless, MD, section head for clinical genetics and metabolism at Children's Hospital Colorado and University of Colorado School of Medicine in Aurora.

 GLWL Research, Inc., a Canadian pharmaceutical company, is testing the efficacy of GLWL-01, a molecule that reduces levels of acylated ghrelin, a hormone associated with satiety. InSys Therapeutics, Inc., a company in Chandler, AZ, is evaluating cannabidiol therapies to see whether they can control the hunger and obsessive behavior of patients with Prader-Willi syndrome. And Soleno Therapeutics in Redwood City, CA, is beginning a phase 3 clinical trial of diazoxide choline controlled-release for appetite suppression.

Meanwhile, Levo Therapeutics is exploring the properties of carbetocin, a drug used to control bleeding after a Cesarean section, for moderating feelings of hunger. The drug is available in Canada and the United Kingdom, but not in the United States. Michigan-based Millendo Therapeutics is preparing to initiate a phase 2b study to test the efficacy of livoletide, a drug that counteracts the effects of acylated ghrelin. An earlier phase 2 double-blind, placebo-controlled, randomized study of 47 patients with Prader-Willi syndrome showed a reduction in feelings of hunger after two weeks.

Promising Research

In a 2017 study published in Diabetes, Obesity and Metabolism, Dr. McCandless and other researchers found that a drug called beloranib helped reduce patients’ appetite and lose weight. Unfortunately, the drug also increased the risk of blood clots, and two people died in the clinical trials. Although the trials were stopped, “this was the first study to prove that you can use medicine to treat the appetite problem,” Dr. McCandless says.

 A paper published in February 2018 in Human Molecular Genetics reported that stem cell researchers at the University of Connecticut had reversed Prader-Willi in brain cells grown in the lab. While this is a great step forward, Dr. McCandless is quick to point out that it’s not a cure. “What they showed is that if you take cells in culture that come from a person with Prader-Willi and you convert them into brain cells, they could reverse the genetic problem in those cells.”

Extended Lifespan

Living longer with Prader-Willi is more likely today than it was 20 years ago, especially if their ability to access food is limited. “Parents or caregivers lock the kitchen or fridge or cupboard,” says Dr. McCandless. “Before we knew how to manage it, most people died in their twenties and thirties from diabetes, sleep apnea, and heart failure. But now we have people living into well past their forties.”