Projects Archive - Foundation for Prader-Willi Research | Hunger Satiety

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 gut microbiome in Prader-Willi syndrome

Funded Year: 2018

Abstract Prader-Willi syndrome individuals show impaired social behaviors and altered oxytocin levels in the brain, but the reason for this remains unknown. Here we will test whether changes in the gut bacterial content in PWS could perturb social behaviors and related changes in oxytocin. In addition, we will examine whether a probiotic bacteria false

Consequences of targeted SNORD116 deletion in human and mouse neurons

Funded Year: 2018

Abstract The role of the brain in controlling food intake is increasingly apparent, with studies finding that genes related to obesity often play a role in brain regions crucial for feeding, appetite, and satiety. Prader-Willi syndrome, one of the most common forms of genetic obesity, results increased food intake (hyperphagia) leading to severe false

Developing objective biomarkers of hyperphagia in children with PWS

Funded Year: 2017

Hyperphagia is one of the distinctive features of Prader-Willi syndrome (PWS), and when not carefully monitored or controlled, can be life threatening. It emerges in early childhood and remains a life-long challenge for individuals with PWS and their caregivers. To effectively manage and, in the future, treat hyperphagia, it is important to be 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.

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

Recapitulating obesity and hyperphagia in novel adult-onset mouse models of Snord116 deletion

Funded Year: 2016

Although it is well established that deletion of SNORD116 contributes to PWS in humans, mice missing Snord116 don’t display hyperphagia and obesity. This makes it very difficult to study the biology of SNORD116 and test anti-obesity drugs. In a major breakthrough, Dr. Yeo’s group has shown that if Snord116 is deleted in adult mice, a percentage of false

Ghrelin: Is it detrimental, beneficial, or inconsequential in Prader-Willi Syndrome? (year 2)

Funded Year: 2016

Ghrelin levels are elevated in PWS, but why, how, and whether it plays a role in hyperphagia or other aspects of PWS are all still unanswered questions. This project will explore if ghrelin plays a protective role in PWS with regards growth hormone deficiency, hypoglycemia and mental health issues, but a detrimental role with regards to extreme false

Loss of MAGEL2 and hypotonia in Prader-Willi syndrome

Funded Year: 2016

Children with PWS are hypotonic (floppy) at birth. Their poor muscle tone causes delays in sitting and walking and contributes to orthopedic problems such as scoliosis. Reduced endurance lowers the number of calories they can consume per day to manage their body weight, and impairs their quality of life. Treatments that build muscle mass or 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

Role of melanin concentrating hormone in an animal model of Prader-Willi Syndrome

Funded Year: 2015

Prader-Willi Syndrome (PWS) is a rare genetic disorder with symptoms that typically include obesity, severe appetite and impaired reproductive function. It is thought that dysfunction of the hypothalamus, a part of the brain that controls body weight and reproduction, underlies some of these symptoms. Our goal is to understand what is false

Characterisation of anti-ghrelin autoantibodies in Prader-Willi Syndrome

Funded Year: 2015

Excessive eating (hyperphagia)  is one of the most challenging features of Prader-Willi Syndrome (PWS) and currently there are no medications available for effective appetite regulation. Hyperphagia is most likely to be driven by elevated levels of the appetite-stimulating hormone ghrelin in patients with PWS. The underlying cause of this elevated false

Ghrelin: Is it detrimental, beneficial, or inconsequential in Prader-Willi Syndrome?

Funded Year: 2015

Plasma levels of the peptide hormone ghrelin are markedly elevated in individuals with Prader-Willi Syndrome (PWS), however the functional consequences of this elevation have not yet been determined, nor are the mechanistic causes of ghrelin elevation known. Many attribute the characteristic, maladaptive PWS eating behaviors directly to ghrelin, false

Linking the cellular function of MAGEL-2 to its role in PWS

Funded Year: 2015

Background: MAGEL-2 is a gene frequently deleted or mutated in individuals affected with PWS. Furthermore, mice lacking MAGEL-2 display symptoms similar to those seen in PWS children. However, a critical barrier to our understanding of MAGEL-2’s link to PWS has been determining its function within cells. Recently, my group has solved this false

Role of the lipid-derived satiety factor, oleoylethanolamide, in PWS

Funded Year: 2014

Prader-Willi Syndrome (PWS) is a complex genetic disorder characterized by an insatiable feeling of hunger and an irrepressible urge to overeat. If left uncontrolled, hunger and overeating can lead to morbid obesity, diabetes, cardiovascular disease and premature death. Why PWS causes hunger is an important question that must be answered in we false

Development of appetite-related neural circuits in a mouse model for PWS (year 2)

Funded Year: 2014

Prader-Willi syndrome (PWS) is a genetic disease characterized by an insatiable appetite and a variety or behavioral dysregulations. It is known that the brain, and particularly a region of the brain called the hypothalamus, is important to regulating appetite and body weight. We also know that many key physiological processes, including appetite 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

Gut microbiome in individuals with PWS

Funded Year: 2014

Prader-willi syndrome is a genetic disorder caused by loss of a portion of a copy of chromosome 15.  Common features include early problems with muscle weakness and feeding followed by occult weight gain without an increase in food consumption beginning during late infancy/early toddler period prior to the onset of hyperphagia.  Recent research 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

Oxytocin vs. placebo for the treatment of hyperphagia in Prader-Willi syndrome

Funded Year: 2013

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by lack of inherited genes from fathers on chromosome 15. PWS is characterized by intellectual disabilities, repetitive and compulsive behaviors, social cognition deficits, increased eating and obesity. These individuals typically consume up to three times the normal caloric 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

The role of the prefrontal cortex in PWS hyperphagia

Funded Year: 2013

Among the many complications of Prader-Willi Syndrome (PWS), the increased food intake (hyperphagia) has serious long-term medical consequences. The goal of this proposal is to define novel brain regions that may contribute to this problem. Studies of brain activity suggest that the prefrontal cortex might be different in PWS patients. This is an false

Development of appetite-related neural circuits in a mouse model for Prader-Willi syndrome (year 1)

Funded Year: 2013

Prader-Willi syndrome (PWS) is a genetic disease characterized by an insatiable appetite and a variety of behavioral dysregulations. It is known that the brain, and particularly a region of the brain called the hypothalamus, is important to regulating appetite and body weight. We also know that many key physiological processes, including appetite false

Development of leptin dysregulation in a mouse model of obesity in PWS

Funded Year: 2013

The brain balances energy stores with energy expenditure with little conscious effort. The hypothalamus is a part of the brain that senses levels of a hormone called leptin, which is produced by fat. Excess leptin normally causes a decrease in appetite and increase in activity. This balance is disrupted in obese children who carry mutations in false

Generating a novel model of ghrelin-null Prader-Willi syndrome

Funded Year: 2011

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by a lack of muscle tone at birth, a failure to thrive in infancy, and mild learning disabilities.   On emerging from infancy, children with PWS show reduced skeletal growth and an insatiable appetite, which, when combined with an obsession with food, results in obesity.   false

A pig model of PWS: a breakthrough for obesity, clinical and therapeutic studies

Funded Year: 2011

Overcoming the severe drive to overeat and obesity that provides the greatest threat to life expectancy and life quality is of upmost and crucial importance for PWS individuals and families. Despite advances in understanding the genetic causes of PWS and the establishment of different mouse models that mimic some clinical components, the false

Role of Kiss1 neurons in mediating grhrelin’s effect on effect on reproduction and metabolism (year 2)

Funded Year: 2011

Prader-Willi syndrome (PWS) is a genetic disorder characterized by impairment of a myriad of physiological systems including growth, development, metabolism and reproduction. Although the physiological deficits observed in individuals with PWS come to be well-recognized, the mechanisms and/or cause for the generation of these characteristics are false

Mechanism of hyperphagia and therapeutic interventions in mouse models for Prader-Willi syndrome

Funded Year: 2011

The overall goals of our research are to elucidate the pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS, and to evaluate two types of treatments for persistent hunger and food seeking behavior. We have focused on the role of a special type of RNA, called Snord116 (formally PWCR1/HBII-85) small nucleolar RNA false

The relationship between serum brain-derived neurotrophic factor (BDNF) levels, BDNF haplotypes and neurocognitive performance in children with PWS

Funded Year: 2010

Prader-Willi Syndrome (PWS) is a genetic disease characterized by failure to thrive and low muscle tone during infancy, followed by food-seeking and severe obesity in childhood. Other manifestations include altered pain perception, cognitive impairment, maladaptive behaviors (obsessive compulsive, temper tantrums, skin picking, rigid thinking and false

MCH neurons in animal models of Prader-Willi syndrome

Funded Year: 2010

Prader-Willi syndrome (PWS) is a disease caused by mutations on human chromosome 15 leading to "floppy" infants initially, and obesity and sleep disorders later. Although genetic defects underlying PWS have been documented, it is still not well understood how the loss-of-function of genes results in various symptoms in PWS. It has been shown that false

Role of Kiss1 neurons in mediating ghrelin’s effect on reproduction and metabolism (year 1)

Funded Year: 2010

Prader-Willi syndrome (PWS) is a genetic disorder characterized by impairment of a myriad of physiological systems including growth, development, metabolism and reproduction. Although the physiological deficits observed in individuals with PWS come to be well-recognized, the mechanisms and/or cause for the generation of these characteristics are 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

Ghrelin and peptide YY levels and gene expression in Prader-Willi syndrome

Funded Year: 2009

Prader-Willi syndrome (PWS) is a complex genetic condition due to imprinting or the differential expression of genetic information depending on the parent of origin. The majority of subjects with PWS have a deletion of chromosome 15q11-q13 region received from the father while others have maternal disomy 15 (both 15s from the mother) or a mutation false

Understanding the action of ghrelin in the brain: Identification of novel treatments for hyperghrelinaemia

Funded Year: 2009

(Year 2 of this project)

Understanding the action of ghrelin in the brain: Identification of novel targets for hyperghrelinemia

Funded Year: 2009

In patients suffering Prader-Willi syndrome it has been shown that there is a greatly elevated level of a hormone known as ghrelin. This hormone is known to normally stimulate hunger and food intake. However, the levels of the circulating hormone leptin that signals the need to reduce food intake and increase energy expenditure is not similarly up false

The role of the midbrain dopaminergic reward circuitry in ghrelin's effects on food intake and body weight

Funded Year: 2009

Prader-Willi Syndrome is a disorder characterized by numerous medical conditions, including excessive eating, low metabolic rate, growth hormone deficiency, hypogonadism and various cognitive deficits. In fact, obese individuals with PWS are described as having a nearly constant state of hunger, which manifests in various maladaptive feeding 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

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