Prader–Willi syndrome (PWS) is a complex neurobehavioral/metabolic disorder which is due to the absence of or lack of expression of normally active paternally expressed genes from the chromosome 15q11-q13 region. PWS can occur due to a de novo deletion in the paternally inherited chromosome region; because the individual inherited two copies of chromosome 15 from their maternal parent; or due to imprinting defects which lead to lack of expression of the genes in the region. Clinical features of PWS include hypotonia and poor feeding in infancy which almost always requires some type of assisted feeding for a period of time. Hypotonia and low muscle mass is present throughout life. The accumulation of excess body fat typically begins around age 2 years if the diet is not restricted. Ultimately, the central neurological defect associated with the condition causes PWS patients to sense that they are starving and signals them to further conserve energy and to significantly increase their caloric intake. PWS patients at this stage are food obsessed and constantly food seeking – they are hyperphagic. They will wake up at night to eat, steal food, bargain for food, steal money to buy food, eat frozen food, pet food, or spoilt food, or consume non-food items. Mental retardation, growth hormone deficiency, behavioral problems, including aggressive behaviors and neuroendocrine abnormalities are also characteristic of PWS.
Prader-Willi Syndrome (PWS) is the most common syndromic form of obesity and may affect between 350,000 and 400,000 individuals worldwide. Both sexes and all races and ethnicities are affected. The Prader-Willi Syndrome Association USA (PWSA [USA]) estimate prevalence at 1 in 15,000 and the Foundation for Prader-Willi Research (FPWR) cites an incidence of 1 in 15,000 births. The International Prader-Willi Syndrome Organization states that between 1 in 15,000 and 1 in 30,000 people have Prader-Willi syndrome and OrphaNet reports a prevalence of 1 to 9 in 100,000 and 1 in 25,000 births.
The death rate among PWS patients has been estimated at 3% per year at all ages, more than twice that of the general population. Among older PWS patients, much of the mortality and morbidity is associated with obesity and diabetes. In infants, the most common cause of death is respiratory failure and/or infection. Once hyperphagia, the hallmark symptom of PWS, presents in children, hyperphagia-related deaths become much more common and include accidents (including those related to hyperphagia and related food seeking behaviors), gastric rupture, choking, and obesity.
As hyperphagia presents, PWS patients become food obsessed, and are constantly food seeking. Food is often locked up and otherwise tightly regulated. This leads to behavioral complications, making the patient difficult to manage, which impacts the caregiver and other family members. Other behavioral complications occur in parallel even if they are not caused by hyperphagia.
Families including children with PWS show poorer perceived quality of life compared with families of children with other complex health conditions. They report difficulties in family functioning, communication problems, and higher numbers of conflicts. They experience significant behavioral distress, with higher than average levels of depression and feelings of isolation, anger and worry. Normal siblings of PWS children may show moderate-to- severe Post-Traumatic Stress reactions.
There is no currently approved therapeutic that effectively controls hyperphagia. The greatest unmet medical need in PWS, as determined by parents and caregivers of PWS patients is to address hyperphagia and problematic food related behaviors. These same parents and caregivers viewed reducing temper outburst severity and frequency as very important.
At Soleno Therapeutics, we are fully committed to developing diazoxide choline controlled-release (DCCR) for treatment of Prader Willi Syndrome (PWS). At present, this therapy is investigational, which means that it has not been deemed to be safe and effective by regulatory health authorities such as the U.S. Food and Drug Administration (FDA).
We believe it is only through the systematic development process, which is shaped by rigorous regulatory approval processes, that we can have the greatest, most positive impact on the patients for whom our therapy is designed to benefit. With these goals in mind, our focus is on directing resources to completing our development program of DCCR to generate the necessary evidence of safety and efficacy required to obtain regulatory approval.
At this time Soleno is not able to make DCCR available outside of our clinical trials. We encourage any PWS patients, and their caregivers, interested in gaining access to any investigational therapy to consult their physician regarding the possibility of participating in clinical trials. A listing of our and other clinical trials can be found on publicly accessible databases such as ClinicalTrials.gov.
This is an exciting time for medical and scientific innovation in PWS, and Soleno is proud to be working toward improving the lives of people affected by this condition.
Footnote: This policy is issued in compliance with Chapter V, Section 561A of the U.S. Federal Food, Drug, and Cosmetic Act.
Additional information on Prader-Willi syndrome can be found at: