Cognitive Improvements in Children with Prader-Willi Syndrome Following Pitolisant Treatment-Patient Reports

Abstract

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.

Keywords: Prader-Willi Syndrome; cataplexy; cognition; narcolepsy; pitolisant; sleep.

Conflict of interest statement

Disclosure Dr Holger Stark is the co-inventor of pitolisant. Maria Picone is the founder of Formed, Inc, a digital health technology company that is developing the TREND Community platform. TREND Community and Chion Foundation have received unrestricted grants from Harmony Biosciences. The other authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all patient information in this report and take responsibility for the integrity and accuracy of the report.

Figures

Figure.

Improved mental clarity and processing speed in response to pitolisant. The figure illustrates the Likert scale indicating parental responses to the weekly questionnaire. 1 = strongly disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = strongly agree