Table 3. Potential treatments to reduce hyperphagia in Prader-Willi syndrome (PWS)

Mechanism of action	Reason for treatment selection	Studies
Oxytocin The brain produces the neuropeptide hormone oxytocin, which is involved in eating behavior, anxiety, energy expenditure, controlling body weight, and social interactions.	It has been noted that PWS patients have fewer neurons that produce oxytocin. Their inability to control their emotions, bad eating habits, and poor social integration may all be related to this deficiency.	[65–72]
Diazoxide choline-controlled release (DCCR) DCCR, a benzothiadiazine, is used to treat hyperinsulinemia-related hypoglycemia in newborns, children, and adults by increasing ion flow through ATP-sensitive K+ channels.	The dysregulation of neuropeptide Y/Agouti-related protein/gamma-aminobutyric acid (NAG) neurons, which are regulated by leptin by decreasing their excitability, is linked to hyperphagia in Parkinson’s disease. The most powerful endogenous neuropeptide, Neuropeptide Y (NPY), is produced and secreted in significant amounts as a result of this imbalance. The hyperpolarization of the resting membrane potential caused by leptin’s activation of ATP-sensitive K+ channels (KATP) via phosphoinositide-3-kinase (PI3-K) limits the release of NPY by these neurons, thereby attenuating the hyperphagia signal.	[39]
Glucagon-like peptide-1 agonist During meals, the pancreas secretes more insulin in response to food consumption, which aids in controlling postprandial glucose levels. The synthesis of glucagon-like peptide-1 (GLP-1) aids in this process.	Studies have investigated how GLP-1 receptor agonists, which delay stomach emptying and decrease appetite, impact weight loss.	[42–44]
Setmelanotide Setmelanotide, an agonist of the melanocortin (MC)-4 receptor, influences feeding and satiety to decrease eating.	Patients with PWS show strong food desire and hyperphagia from an early age, and eventually develop excessive obesity if their condition is not treated externally.	[45–47]
Livoletide Livoletide is an inactive analog of ghrelin that works by lowering the amount of the active form of ghrelin in the brain. The stomach produces a neuropeptide known as ghrelin, which triggers the human hypothalamus to directly stimulate appetite.	PWS patients have higher ghrelin levels.	[48–50,69]
Cannabinoids The control of appetitive behavior is significantly influenced by the cannabinoid-1 receptor (CB1R).	Cannabinoids have an anti-obesity effect because of their antagonistic impact on CB1R.	[51]
Beloranib In animal models, beloranib inhibits methionine aminopeptidase 2 (MetAP2) by removing methionine residues from proteins, thereby impacting adipocyte development and fat metabolism.	It has been discovered that MetAP2 inhibitors lower food intake, impact adipose tissue, and decrease fat production during weight reduction in people.	[73]
Transcranial direct-current stimulation (tDCS) tDCS is a method of modifying neural and cognitive performance in specific brain regions to help control food cravings. It is painless, safe, and non-invasive.	The dorsolateral prefrontal cortex is a brain region that mediates the processing and regulation of human food appetites and motivation.	[53–55]