While children with
Prader-Willi Syndrome (PWS), a rare
genetic disease with an incidence of 1:15,000, typically present with
hypotonia and
hyperphagia, their lives are made more difficult by an ever-present
sleepiness as well as multiple neuro-
cognitive dysfunctions, including cognitive defects. We describe a case series of 3 children who were treated with the
histamine 3 receptor inverse agonist
pitolisant. While this first-in-class inverse agonist is approved for another
orphan disease (i.e.,
narcolepsy with or without
cataplexy), we have observed that pediatric patients with PWS prescribed
pitolisant demonstrate decreased
daytime sleepiness and improved cognition, as evidenced by increased processing speed and improved mental clarity.
Pitolisant may represent a novel therapeutic option that might relieve substantial PWS disease burden, including cognitive disability,
excessive daytime sleepiness, and poor-quality nighttime sleep.