Table 1.

Summary of drugs and medical devices used in PWS clinical trials.

Mechanism of Action	Studies Reviewed	Age Range	Reason Chosen for Treatment
Beloranib Beloranib inhibits methionine aminopeptidase 2 (MetAP2) by removing methionine residue from proteins, impacting fat metabolism and adipocyte size in animal models.	McCandless et al. [15]	12–65 years	Inhibitors of MetAP2 were found to reduce food intake, affect adipose tissue, and reduce fat synthesis with weight loss in humans.
Oxytocin Oxytocin is a neuropeptide hormone produced in the brain that plays an important role in social interactions and skills, food intake, anxiety, energy expenditure, and body-weight regulation.	Tauber et al. [22] Einfeld et al. [23] Kuppens et al. [24] Miller et al. [25] Tauber et al. [26] Damen at al. [27] Hollander et al. [28]	18.7–43.6 years >12 years 6–14 years 5–11 years <6 months 3–11 years 5–18 years	Patients with PWS have been reported to have decreased oxytocin-producing neurons. This deficiency could be related to their inability to control their emotions, with poor social adjustment and food intake.
Setmelanotide Setmelanotide is a melanocortin (MC)-4 receptor agonist that impacts satiety and feeding to decrease eating.	Rhythm Pharmaceuticals [29,30,31]	16–25 years	Patients with PWS begin marked food seeking and hyperphagia during early childhood and develop extreme obesity over time if not externally controlled.
Diazoxide choline controlled release (DCCR) DCCR is a benzothiadiazine that acts by stimulating ion flux through ATP-sensitive K+ channels used to treat infants, children, and adults with hyperinsulinemia hypoglycemia.	Kimonis et al. [40]	10–22 years	Hyperphagia in PWS relates to dysregulation of neuropeptide Y/Agouti Related Protein/Gamma-aminobutyric Acid (NAG) neurons, which are regulated by leptin via the reduction of their excitability. This dysregulation results in marked elevations in the synthesis and secretion of NPY, the most potent endogenous neuropeptide. Leptin’s activation of adenosine triphosphate (ATP)-sensitive potassium channels (KATP) via phosphoinositide-3-kinase (PI3-K) serves to hyperpolarize the resting membrane potential, resulting in a limitation of the release of NPY by these neurons, thus blunting the hyperphagia signal.
Livoletide Livoletide is an inactive ghrelin analogue which works by decreasing the amount of the active form of ghrelin in the brain. Ghrelin is a neuropeptide produced by the stomach which directly stimulates eating behavior in the hypothalamus in humans.	Millendo Therapeutics SAS [42]	8–65 years	Patients with PWS have elevated ghrelin levels.
Exenatide Glucagon-like peptide-1 (GLP-1) is a hormone synthesized from L- cells of the ileum and colon and released in response to food intake. GLP-1 receptor agonists such as Exenatide affect weight loss in the form of a delay in gastric emptying and decreased appetite.	Salehi et al. [45]	13–25 years	Exenatide is a GLP-1 receptor agonist and its use has resulted in persistent weight loss in animals and obese adults.
Transcranial direct-current stimulation (tDCS) Transcranial direct-current stimulation (tDCS) is a safe, painless, and non-invasive technique to modify neuronal and cognitive function in areas of the brain to help modulate food craving.	Bravo et al. [46] Poje et al. [48] Gabrielli et al. [49]	18–64 years 19–44 years 16–65 years	The dorsolateral prefrontal cortex (DLPFC) is involved in the regulation and processing of food craving and motivation in humans.