Projects Archive - Foundation for Prader-Willi Research | Therapeutic Development

Under the guidance of our Scientific Advisory Board through a carefully managed grants process, FPWR selects research projects based on the collaborative input of researchers and parents, choosing projects that are both scientifically meritorious and highly relevant for individuals with PWS and their families.

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The molecular mechanism of SNORD116 action (year 2)

Funded Year: 2018

Abstract SNORD116 is a C/D box small nucleolar RNA that is critical for the etiology of PWS, as microdeletions encompassing only SNORD116 cause a PWS-like phenotype. The molecular functions of SNORD116 have been elusive, preventing therapy design. We showed that SNORD116 is not a typical snoRNA, as it associates with different proteins and has a false

Comufaces: The Perception of Communicative Faces by Infants with PWS (Year 2)

Funded Year: 2018

Neuropsychological studies have detailed several cognitive deficits in Prader-Willi Syndrome (PWS), among which the observation of altered social interactions, with notable difficulty in interpreting and responding to social information. The integration of the information from the face and the voice is important for our social communication as false

Systematic Investigation of Early Social Cognitive Processes and the Feasibility of Intervention

Funded Year: 2017

For Year 1, our project aims were: 1) to characterize the social, cognitive, and affective processes in preschoolers with PWS (by genetic subtype), in comparison to preschoolers with ASD and typically developing children, and 2) to pilot a remotely delivered parent education program to determine if it would be feasible and effective for families false

Neural mechanisms of oxytocin-enhanced infant feeding and social behavior development

Funded Year: 2017

This project uses infant mice to understand the mechanism of a promising treatment for PWS. Oxytocin (OXT) regulates feeding and social behavior. In mouse research and recent clinical trials with infants and young children, OXT seems to improve the core feeding and social behavior disturbances of PWS. In humans, OXT is effective when it is given false

Dissecting a novel brainstem feeding circuit in Prader-Willi syndrome

Funded Year: 2017

There is currently no cure for Prader-Willi syndrome (PWS). PWS is a complex and debilitating disorder that significantly impacts the lives of not only affected patients, but their families, as well. Recent work has revealed a genetic basis for PWS, and a number of the genes affected are known to have unique expression patterns throughout the false

Therapeutic Potential of Blocking Zinc Finger Protein 274 Binding to the PWS Locus

Funded Year: 2017

Our goal is to understand the molecular pathways disrupted in Prader-Willi syndrome (PWS) and to develop therapeutic interventions for this disorder. Through the biological process called genomic imprinting, the chromosome 15 that is inherited from the father has a set of genes that is switched on while the same set of genes on the chromosome 15 false

Evaluating factors that may affect the efficacy of intranasal oxytocin treatment in PWS

Funded Year: 2017

Recent studies with oxytocin treatment in PWS have yielded inconsistent results. Intranasal administration of oxytocin by the Toulouse group decreased disruptive behaviors in patients with PWS, but a recent randomized trial in Australia of adolescents and adults of intranasal oxytocin (IN-OT) found no effect on syndrome-specific behavior in false

Transcranial direct current stimulation, startle modulation and event-related potentials of the brain

Funded Year: 2017

Hyperphagia (extreme overeating) is the most significant factor contributing to obesity in Prader-Willi syndrome (PWS) and considered a cardinal feature. PWS is recognized as the most common syndromic cause of life-threating obesity, but no medications are currently available to decrease appetite or lessen obesity in PWS.

Proof of concept study of vagus nerve stimulation from an external device in PWS (year 2)

Funded Year: 2017

The hypothesis set out in our original application is that t-VNS given over time and following a protocol established for its use in epilepsy, will prevent the prolonged and debilitating temper outbursts and associated emotional dysregulation that characteristically affect people with PWS. We further propose that any improvements in behavior are false

Small molecule allosteric modulators of the melanocortin-4 receptor for the treatment of Prader-Willi syndrome

Funded Year: 2016

There is some data suggesting that one of the systems that regulates appetite and weight in the brain, the melanocortin-4 receptor pathway, may be disrupted in PWS.  This study will examine a new class of drugs targeting this pathway, in a mouse model of PWS.  The drugs will be tested alone and in combination with other drugs currently being false

The molecular mechanism of SNORD116 action and possible SNORD116 substitution strategies

Funded Year: 2016

The loss of two snoRNAs, SNORD115 and SNORD116, plays a central role in the development of Prader-Willi syndrome. However, the normal function of SNORD116 is still unclear, making it difficult to understand what goes wrong when SNORD116 is lost. Dr. Stamm’s group is exploring how SNORD116 influences other genes, and their preliminary studies false

Preclinical studies of a novel epigenetic therapy for Prader-Willi syndrome

Funded Year: 2016

Despite the significant progress in understanding the molecular basis underlying Prader-Willi syndrome, little advance has been achieved in developing the treatment specifically targeting to the molecular defect. The SNORD116 between the SNRPN and UBE3A genes is important for the major features of PWS. The host transcripts and SNORD116 in the false

Mitochondrial Complex I dysfunction in Prader Willi Syndrome: A new therapeutic target

Funded Year: 2016

Children with Prader-Willi syndrome suffer from very low muscle tone, growth delay, short stature, developmental delay, muscle weakness and exercise intolerance. Studies have suggested that there is a problem with energy metabolism in PWS but what kind of problem this is and how this leads to PWS is not clear at the present time. Many PWS patients false

Plastic TASTER: a switching training game for people with PWS that adapts to individual needs (year 2)

Funded Year: 2016

Task switching is a cognitive process important for regulating behaviour. People with PWS generally show impaired switching and this difficulty is linked to people resisting change and showing temper outbursts triggered by changes.

Oxytocin treatment in Magel2-defcient mice (year 2)

Funded Year: 2016

The MAGEL2 gene appears as one of the main genes involved in feeding and behavioral (autistic like behavior) alterations observed in Prader-Willi Syndrome. We showed that, in mouse, the deficiency of Magel2 results in a phenotype similar to the clinical description of patients with mutations in MAGEL2. Indeed, we showed that Magel2-deficient mice false

Evaluating the Parent-focused Remote Education To Enhance Development (PRETEND) Program in PWS

Funded Year: 2015

This project centers on better understanding the social-cognitive characteristics of Prader-Willi syndrome (PWS) in early childhood and providing education and training to parents of children with PWS to optimize learning and joint engagement between parent and child. There are two goals of this research:

Proof of concept study of vagus nerve stimulation from an external device In Prader Willi Syndrome

Funded Year: 2015

This proposed proof of concept study follows an earlier trial of vagus nerve stimulation, using a surgically implanted medical device, in three people with PWS to investigate whether such treatment might reduce the over-eating behaviour characteristic of people with PWS. Whilst the effects on eating were equivocal, two of the three participants, false

Oxytocin and the autonomic nervous system in Prader Willi syndrome

Funded Year: 2015

Study one: There is a reduction in the number of neurons that produce oxytocin in people with PWS. This, along with a range of other evidence supports the likelihood that abnormalities in the oxytocin system are key to the problems of PWS. However, studies examining the levels of oxytocin in PWS as well as clinical trials evaluating the effect false

Development and validation of ghrelin O-acyltransferase inhibitors for treating hyperphagia in Prader-Willi syndrome

Funded Year: 2015

Obesity and insatiable appetite (hyperphagia) are among the most serious symptoms experienced by Prader-Willi syndrome (PWS) patients. While many of the causes underlying PWS symptoms remain unknown, the discovery of the protein hormone ghrelin and its role in controlling appetite has led researchers to investigate the possible role of ghrelin in false

Rapamycin treatment to correct the circadian mTOR imbalance in the Snord116 deletion mouse model of PWS

Funded Year: 2015

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder with a known genetic etiology, but a complex epigenetic basis.  PWS is an imprinted disorder, meaning that the genes implicated in PWS are expressed only on the paternal but not the maternal chromosome 15q11-13. At the heart of the minimally deleted region in PWS are several processed false

ComuFaces: The perception of communicative faces by infants with Prader-Willi syndrome

Funded Year: 2015

Paying attention to communicative faces is essential for our understanding of the social world. Indeed, faces provide observers rich and complex information about the identity (gender, age, etc), the socio-emotional state (eye-brows movements, eye-gaze) and the linguistic message (auditory speech sounds/mouth movements) of our social partners. The false

Regulation of ghrelin and serotonin receptors by SNORD115

Funded Year: 2015

The loss of two regulatory RNAs is critical for the development of Prader-Willi syndrome. One of these RNAs prevents the formation of a truncated serotonin receptor. We will test the role of this truncated serotonin receptor in the production of growth hormones and determine whether it is a 'master regulator' for other receptors. Based on our false

Training task switching to decrease temper outbursts in people with PWS

Funded Year: 2014

Temper outbursts are commonly shown by people with Prader-Willi syndrome (PWS) and can cause great problems for people with the syndrome, their family members and caregivers. One common reason for temper outbursts is that people with PWS find changes to routines or to plans very difficult. This difficulty with change is linked to impairment in a false

The role of PREPL in the pathophysiology of PWS: evaluation of a novel therapeutic approach for the treatment of hypotonia

Funded Year: 2014

A remarkable clinical resemblance between Prader-Willi syndrome (PWS) and hypotonia-cystinuria syndrome (HCS) was observed in our multidisciplinary clinic for PWS in our center. All HCS patients were initially referred for genetic analysis of PWS. Patients with either syndrome suffer from weakness and poor sucking in the newborn period. This false

Transcranial direct current stimulation, startle modulation and event-related potential of the brain to evaluate hyperphagia in PWS

Funded Year: 2014

Hyperphagia (extreme overeating) is the most significant factor contributing to obesity in Prader-Willi syndrome (PWS) and considered a cardinal feature.  PWS is recognized as the most common syndromic cause of life-threating obesity, but no medications are currently available to decrease appetite or lessen obesity in PWS. Preliminary studies have false

Injectable protein gene activation therapy for PWS (year 2)

Funded Year: 2014

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human chromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS false

A Dose Titration Study of Diazoxide Choline Controlled-Release Tablet (DCCR) in Patients with Prader-Willi syndrome with a Double-Blind, Placebo-Controlled, Randomized Withdrawal Extension

Funded Year: 2014

Once Prader-Willi patients reach the stage where hyperphagia is a dominant characteristic of the disease, the progression to obesity, morbid obesity and diabetes and their complications reduces the quality of life of the patient and increases their risk of death from a number of causes. The constant food seeking and food obsession combined with false

Investigation of ghrelin-o-acyltransferase as a target for treating hyperphagia in Prader-Willi syndrome (Year 1)

Funded Year: 2013

Obesity and insatiable appetite (hyperphagia) are among the most serious symptoms experienced by Prader-Willi syndrome (PWS) patients.  While many of the causes underlying PWS symptoms remain unknown, the discovery of the protein hormone ghrelin and its role in controlling appetite has led researchers to investigate the possible role of ghrelin in false

Support to develop a grant application for a cross-over controlled trial of vagus nerve stimulation (VNS) in PWS

Funded Year: 2013

The vagus nerve is a major route of communication between the brain and the gut. Vagus nerve stimulation (VNS) is a procedure whereby a small implanted device placed under the skin on a patient’s chest delivers an intermittent electrical impulse to the vagus nerve, which will travel up and down the nerve and into the brain and to the gut. VNS has false

Early to midterm oxytocin effects on the brain metabolism of adults with Prader-Willi syndrome (year 2)

Funded Year: 2013

This supplement will help Dr. M. Tauber complete the study awarded in 2011: Early to midterm oxytocin effects on the brain metabolism of adults with Prader-Willi syndrome. Prader-Willi syndrome (PWS) is a rare multisystem genetic disease leading to severe disabilities such as morbid obesity, as well as behavioral and socialization problems. We are false

Oxytocin actions of prefrontal cortex circuits in a mouse model of Prader-Willi Syndrome

Funded Year: 2013

Mental illness is a major problem in Prader-Willi syndrome (PWS). It prevents social interactions and seriously threatens the quality of life of the patient and of those around the patient. Mood swings, stereotyped repetitive behaviors, psychotic episodes are dependent on proper functioning of brain regions such as the prefrontal cortex. Activity false

Functional Assessment of snoRNA derived microRNAs in Prader-Willi Syndrome

Funded Year: 2013

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder, predominantly caused by a deletion on the long arm of chromosome 15. This deletion eliminates a group of genes called HBII-85 whose function is currently unknown. Therefore, this proposal aims to investigate the underlaying molecular mechanisms behind the loss of HBII-85 and how this false

Targeting the peripheral endocanniabinoid system for the treatment of obesity in a mouse model of PWS

Funded Year: 2013

Extreme obesity is one of the major health problems related to Prader-Willi syndrome (PWS), yet there are few effective medications. Endocannabinoids (eCBs) are lipid signaling molecules that act on a cellular receptor, called the CB1 receptor. This receptor is present in the brain and in peripheral tissues, where it also recognizes the false

Evidence based approach to dietary management of PWS

Funded Year: 2013

Lay Abstract: Prader-Willi Syndrome (PWS) is a genetic disease characterized by failure to thrive and low muscle tone during infancy, followed by food-seeking, insatiable appetite and progressive obesity in childhood. The resulting increases in total body fat and decreases in muscle mass lead to metabolic problems such as diabetes and heart false

Reactivation of maternally-silenced genes in PWS

Funded Year: 2013

This proposal will investigate the development of a gene therapy for Prader-Willi syndrome (PWS). PWS is caused by the loss of a region of human cromosome 15q11-13. Humans have two copies of chromosome 15, one the mother (maternal) and one from the father (paternal). Due to an unusual mechanism called genetic imprinting, the genes affecting PWS false

Small molecular screening and therapeutic potential for PWS

Funded Year: 2013

Like most genetic disorders, there is no specific therapeutic intervention targeted to the molecular defect for Prader-Willi syndrome (PWS). The clinical presentations of PWS are caused by paternal deficiency of genes in the chromosome 15q11-q13 region. Recent reports indicate a region between the SNRPN and UBE3A genes harboring SnoRNA clusters is false

Early to midterm oxytocin effects on the brain metabolism of adults with Prader-Willi syndrome

Funded Year: 2012

Prader-Willi  syndrome  (PWS)  is  a  rare  multisystem  genetic  disease  leading  to  severe disabilities such as morbid obesity, as well as behavioral and socialization problems. We are greatly lacking in information on the natural history of this complex disease and the factors involved in its progression and outcome. Early diagnosis and a false

The 5-HT2CR: Mining a new experimental approach to therapeutics for Prader-Willi syndrome

Funded Year: 2010

Prader-Willi Syndrome (PWS) is a complex genetic disorder in which several genes are missing or not functional. PWS is characterized by initial loss of muscle tone and failure to thrive neonatally; children with PWS develop behavioral and cognitive problems, reproductive defects, and excessive overeating. A major medical concern is the morbid false

Plasma oxytocin and other appetite-regulating hormones in Prader-Willi syndrome before and after treatment with intranasal oxytocin

Funded Year: 2009

Prader Willi Syndrome is characterized by a range of well-recognised symptoms including overeating and other food obsessions, rage attacks or tantrums, skin-picking, obsessions, abnormalities of sleep breathing and body temperature, and diificulties in learning and understanding social cues. These difficulties have serious impacts on the health of false

Exenatide: A potential treatment for hyperphagia and obesity in persons with Prader-Willi syndrome

Funded Year: 2009

Prader-Willi Syndrome (PWS) is a condition characterized by growth hormone deficiency, hypogonadism, various behavioral disturbances, an insatiable hunger drive and excessive eating leading to life-threatening obesity. The specific causes of the disturbed eating behavior in persons with PWS remain unknown. More importantly, effective therapies for false

Exploring the potential of using demethylation drugs to treat PWS

Funded Year: 2009

More than 95% of Prader-Willi syndrome (PWS) cases are caused by either a large deletion of paternal chromosome 15q11-q13 or maternal uniparental disomy (UPD) of chromosome 15. The major gene or genes responsible for PWS are subject to genomic imprinting and exclusively expressed from paternal chromosome. For patients with a large chromosomal false

PYY and PP: Potential targets for co-treatment against hyperphagia and obesity

Funded Year: 2009

An insatiable appetite, in conjunction with a low metabolic rate, means that obesity and all of its associated health risks are common in people with Prader-Willi syndrome. Overeating is one of the main barriers to independent living I adults with Prader-Willi syndrome. Moreover, attempts to control their food intake often lead to exacerbation of false

Behavioral treatment of obsessive-compulsive symptoms

Funded Year: 2009

Obsessive-compulsive (OC) symptoms are often present among youth with Prader-Willi Syndrome (PWS). They are also associated with considerable problems in the daily functioning of the child and his/her family. Although medication and behavioral treatments exist that target OC symptoms among youth without PWS, these treatments have not been false

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