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

The purpose of this project is to develop a cellular assay specific to circadian rhythm defects identified by the Reiter laboratory. The eventual goal is to use this assay to screen for compounds that can normalize these circadian defects, potentially identifying drugs that would address developmental and metabolic changes that accompany...

Currently, hyperphagia is often assessed by proxy informants on the Hyperphagia Questionnaires. Leveraging insights from previous research -- and with input from a PWS Advisory Board, PWS focus groups and our own experience in developing other PWS-specific measures—this project will develop a self-report measure of hyperphagic symptoms for...

This proposal investigates the development of a potential epigenetic therapy for PWS. Year 1 of this project showed the researchers were able to reactivate several maternal silenced PWS genes. In year 2, they will determine the epigenetic requirements for a uniform and stable reactivation of the maternal PWS region in human cells using transient...

This study builds on the previous work of Dr. Godler, who developed a high throughput, economical test to detect chromosome 15 disorders in blood spots from newborns. Dr. Wheeler will transfer the technology to a newborn screening program in North Carolina to assess the feasibility of incorporating detection of chromosome 15 disorder into a...

Currently, there are no objective biomarkers of hunger/satiety for PWS, which can be a barrier in PWS research. This study aims to develop an objective biomarker for altered satiety and hyperphagia in PWS using an eye-tracking method (measuring where a person is looking) to measure attentional bias (AB; increased attention) to food. Previously,...

PWS is not the result of a single gene mutation but rather is caused by the loss of several contiguous genes, some of which interact with each other. In this project, Drs. Bouret and Muscatelli will study a new mouse model that lacks two PWS genes, Magel2 and Necdin. The goal is to understand how Magel2 and Necdin act together to influence brain...

In this project, Dr. Nicholls will begin studies towards an innovative gene therapy strategy for PWS, by developing a single adeno-associated virus (AAV)-vector that incorporates up to 80% of the PWS genes. This project will generate miniaturized components from the PWS genes and build an AAV vector carrying eight PWS genes. Delivery and...

Dr. Cao has been developing a gene therapy approach that addresses the major symptoms of PWS, through the delivery of a gene that modulates metabolism and behavior (Brain-derived neurotrophic factor, or BDNF). In her 2nd year of funding, her team will assess whether this single-dose viral gene therapy into brain improves metabolism and behavior...

While we know the loss of SNORD116 (a gene that encodes many snoRNA molecules on Chromosome 15) leads to characteristics of PWS, we do not know how this exactly works. We need to understand how SNORD116 functions normally in order to understand why the loss of this region leads to PWS. It is likely that the snoRNAs in the SNORD116 region modify...

Dr. Reiter is analyzing neurons, made from stem cells from individuals with PWS.  He has noted disruptions in the circadian rhythm of these cells (day/night cycle) that may reflect sleep problems in PWS.  His work will identify how the circadian rhythms are disrupted in PWS cells, and pave the way for identifying new drugs to normalize circadian...

This grant supports a new collaboration between two scientists with complimentary expertise. Drs. Sebastian Bouret and Francoise Muscatelli will work to define critical periods for oxytocin use in PWS models, and optimize this therapeutic approach. Mouse models will be used to define the critical period during which oxytocin might provide the...

Dr. Kurrasch is studying whether inflammation in the brain, mediated by special immune cells called microglia, might contribute to hyperphagia and obesity in PWS. Using a mouse model of PWS, she will examine microglia activity and explore whether eliminating microglia improves energy regulation. Funding provided by FPWR – Canada.

Universal newborn screening for PWS will ensure that all babies with PWS are diagnosed at birth. Dr. Godler has developed a sensitive, accurate and cost-effective DNA test for detection of PWS and Angelman syndrome using the bloodspots (“heelprick”) obtained in all newborns.  In the study, FPWR is collaborating with with the Angelman Syndrome...

This project takes the first steps towards developing a primate (macaque) model of PWS. Animal models of PWS are currently limited and are not able to replicate some important aspects of PWS, such as intellectual disability, as well as behavioral and social impairments. These aspects of PWS may be more effectively studied in a primate model....

This study will combine advanced brain imaging technology with other assessments to examine how hormonal, cognitive, and psychological factors are interrelated in PWS. Results from this study will increase the understanding of how brain regions involved in food intake are related to appetite hormones, hair cortisol, and neuropsychological...

This grant supports the development of a new drug to tackle hunger and obesity with PWS. Inversago, a newly started, specialized biotech company, proposes that its CB1 blockers would treat a wider spectrum of symptoms than anything presently in development for PWS. The drug targets the endocannabinoid pathway, which is known to be altered in...

Overcoming the strong drive to overeat and obesity with negative impacts on life expectancy and life quality is of upmost and crucial importance for individuals with Prader-Willi syndrome (PWS) and their families. Despite advances in understanding the genetic causes of PWS and the establishment of different mouse models that mimic some clinical...

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...

Deletions on chromosome 15 in the bands labeled 15q11.2-q13 on the chromosome inherited from a subject’s father cause Prader-Willi syndrome (PWS). The unique nature of this causative genetic event has been known for many years, but the precise manner in which it causes the developmental abnormalities of PWS is not completely understood since the...

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...

Prader-Willi syndrome (PWS) is a severe neurodevelopmental disorder found in ~1 in 15,000 to 20,000 births. PWS phenotype caused by the loss of function of several genes located on chromosome 15. These genes are usually ‘switched on’ on the chromosome 15 that is inherited from the father and ‘switched off’ on the chromosome 15 inherited from the...

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...

Numerous hormone levels are deficient in PWS. However, the underlying biology and how the altered hormone levels contribute to the characteristics of PWS is not well understood. Dr. Nicholls’ group has developed a novel cell culture model system to study how PWS genes regulate hormone production and release. This model system will advance our...

Recent technological developments have ushered in a new era for the medical research field based on our ability to generate stem cells (called induced pluripotent stem cells or iPSCs) out of adult patient cells, such as blood or skin fibroblasts. There are two important benefits of this technology relevant for research into Prader Willi Syndrome...

There are two goals to this study: 1) To identify differences among individuals with PWS and autism from those who have PWS without autism by analyzing gene expression and 2) To identify new patterns of gene expression which may help explain the PWS condition or how other very small molecules that do not make protein (non-coding RNAs) implicated...

Prader-Willi syndrome (PWS) is caused by a loss of genes normally expressed only from the paternal chromosome 15. About 70% of PWS cases arise from Type 1 and Type 2 deletions, which are about 5 million DNA base pairs in size. Genetic mapping data from unique patients harboring smaller deletions, “microdeletions”, in the PWS region implicate the...

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...

The identification of genetic loci conferring susceptibility to Prader-Willi Syndrome (PWS) provides valuable opportunities for understanding its biological basis. A powerful approach for probing the roles of genes within the nervous system is to introduce them into mice. The resulting mouse models may be studied in depth to determine how genes...

Ariana Garagozzo is not just a future scientist; she is also the sibling of a young man with Prader-Willi syndrome.  As an undergraduate student at Dickinson College, Ariana’s passion to find a cure for hyperphagia has clearly defined her path towards a medical career in PWS research!

Prader-Willi syndrome (PWS) is caused by a loss of genes normally expressed only from the paternal chromosome 15. About 70% of PWS cases arise from Type 1 and Type 2 deletions, which are about 5 million DNA base pairs in size. Genetic mapping data from unique patients harboring smaller deletions, “microdeletions”, in the PWS region implicate the...

Previous results showed that our physical rehabilitation program could induce weight loss in a group of adult PWS patients, but failed to improve their muscular mass (Grolla et al.2010). The loss of muscle mass affects elderly, obese and PWS patients leading to frailty and impaired quality of life. It is becoming apparent, using animal models,...

Prader-Willi syndrome (PWS) is caused by a loss of expression of specific genes normally expressed only from paternal alleles on chromosome 15. PWS patients display common symptoms, which include feeding difficulties in infancy, loss of muscle tone, rapid weight gain after two years of age, extreme hunger and unrelenting appetite, obesity, and...

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.  ...

Two lines of evidence are promoted this proposal. First, recently, smaller microdeletions in the region between the human SNRPN and UBE3A genes have been reported in several cases with features consistent with PWS, including childhood obesity, hyperphagia, and hypogonadism. Second, interestingly, recent studies of genomewide survey of imprinting...

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...

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...

A better understanding of the causes of Prader-Willi syndrome (PWS) and the discovery of potential therapies has been hampered by the unavailability of live tissues. In our laboratory (Marc Lalande), we have established induced pluripotent stem cell (iPSC) technology to create models of human disease in a test tube/tissue culture dish. Skin cells...

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...

Infants with Prader-Willi syndrome (PWS) often suffer failure to thrive that gives way to obesity and excessive eating (hyperphagia) during early childhood. The syndrome is due to the absence of several genes on chromosome 15. Animal models can be used to investigate the etiology of the syndrome and to test potential therapies. Several mutations...

The overall goals of our research are to elucidate the genetic and pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS. We have focused on the role of a special type of RNA, called PWCR1/HBII85 small nucleolar RNA (snoRNA), that was discovered in our laboratory. Studies of rare cases of PWS with smaller deletions and...

The overall goals of our research are to elucidate the genetic and pathophysiologic pathways that lead to the metabolic and behavioral changes in PWS. We believe that a detailed level of understanding is necessary to design rational interventions. Recently, our laboratory has focused on the role of a special type of RNA, called PWCR1/HBII-85 small...

Mammals have two copies of most genes, one copy having been inherited from each parent. While most genes are expressed equally from both parental copies, some genes are expressed from only one parent's copy. Genes involved in Prader-Willi syndrome are normally expressed exclusively from the chromosome inherited from the father, and PWS patients...