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.

Given the severe and rapid impact of COVID-19, the pace of information sharing has been accelerated. However, traditional methods of disseminating and digesting medical information can be time-consuming and cumbersome. In a pilot study, the authors used social listening to quickly extract information from social media channels to explore what people with COVID-19 are talking about regarding symptoms and disease progression. The goal was to determine whether, by amplifying patient voices, new information could be identified that might have been missed through other sources. Two data sets from social media groups of people with or presumed to have COVID-19 were analyzed: a Facebook group poll, and conversation data from a Reddit group including detailed disease natural history-like posts. Content analysis and a customized analytics engine that incorporates machine learning and natural language processing were used to quickly identify symptoms mentioned. Key findings include more than 20 symptoms in the data sets that were not listed in online lists of symptoms from 4 respected medical information sources. The disease natural history-like posts revealed that people can experience symptoms for many weeks and that some symptoms change over time. This study demonstrates that social media can offer novel insights into patient experiences as a source of real-world data. This inductive research approach can quickly generate descriptive information that can be used to develop hypotheses and new research questions. Also, the method allows rapid assessments of large numbers of social media conversations that could be applied to monitor public health for emerging and rapidly spreading diseases such as COVID-19.

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IntroductionSLC6A1 Neurodevelopmental Disorder (SLC6A1-NDD), first described in 2015, is a rare syndrome caused by a mutation in the SLC6A1 gene which encodes for the GABA Transporter 1 (GAT-1) protein. Epilepsy is one of the most common symptoms in patients and is often the primary treatment target, though the severity of epilepsy is variable. The impact of seizures and other symptoms of SLC6A1-NDD on patients and caregivers is wide-ranging and has not been described in a formal disease concept study.MethodsA literature search was performed using the simple search term, “SLC6A1.” Papers published before 2015, and those which did not describe the human neurodevelopmental disorder were removed from analysis. Open-ended interviews on lived experiences were conducted with two patient advocate key opinion leaders. An analysis of de-identified conversations between families of people with SLC6A1-NDD on social media was performed to quantify topics of concern.ResultsPublished literature described symptoms in all of the following domains: neurological, visual, motor, cognitive, communication, behavior, gastrointestinal, sleep, musculo-skeletal, and emotional in addition to epilepsy. Key opinion leaders noted two unpublished features: altered hand use in infants, and developmental regression with onset of epilepsy. Analysis of social media interactions confirmed that the core symptoms of epilepsy and autistic traits were prominent concerns, but also demonstrated that other symptoms have a large impact on family life.DiscussionFor rare diseases, analysis of published literature is important, but may not be as comprehensive as that which can be gleaned from spontaneous interactions between families and through qualitative interviews. This report reflects our current understanding of the lived experience of SLC6A1-NDD. The discrepancy between the domains of disease reported in the literature and those discussed in patient conversations suggests that a formal qualitative interview-based disease concept study of SLC6A1-NDD is warranted.

Background: Disorders of sleep-wake stability have a negative impact on patient and caregiver quality of life. There is evidence that sleep disorders and their sequelae may be an underrecognized burden for people living with rare diseases. Given that the sleep-wake cycle is regulated via the hypothalamus, people with neurological disorders may be particularly affected. To collect real-world insights into the impact of sleep disturbances and excessive daytime sleepiness (EDS) on people with rare disorders, Harmony Biosciences organized a Summit on Sleep Disruption. The attendees were from seven patient advocacy groups, each representing a rare neurological disorder reporting sleep disturbances, specifically EDS: Angelman syndrome, idiopathic hypersomnia, Kleine-Levin syndrome, myotonic dystrophy, narcolepsy, Prader-Willi syndrome, and Smith-Magenis syndrome. One person represented COMBINEDBrain, a patient advocacy consortium representing 25 rare, genetic neurological disorders. Results: The overwhelming response was that disordered sleep, particularly EDS, is a major health problem within their populations that they feel is not adequately diagnosed or treated. Participants felt that burdens associated with sleep disturbances were underrecognized as a treatable medical issue and were not effectively addressed by health care providers. Participants noted the following unmet needs: patient and physician education on sleep disturbance, effective medications approved for these disease populations, and medically acceptable patient-centered devices to measure sleep parameters. Participants described impacts of disordered sleep and EDS on behavior and school performance, describing impaired wakefulness as an interference with normal daytime functioning. Participants also revealed tremendous burdens on the caregivers and family members who live with people experiencing sleep-wake instability. Conclusions: These results provide real-world insights that disordered sleep including EDS and subsequent impaired daytime functioning are major burdens in these rare disease communities. Furthermore, these burdens are underrecognized for caregivers and, for some rare diseases, among the patients themselves. Participants identified gaps in knowledge and treatment of sleep disorders and resolved to continue the dialog to find ways to raise awareness of disordered sleep and reduce burdens in these patient populations.