Projects Archive - Foundation for Prader-Willi Research | Endocrinology/Growth Hormone

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...

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...

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...

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...

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...

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...

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...

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,...

Dr. Tauber is leading a European effort to collect blood samples on infants and children with PWS to monitor changes in hormones over time. This funding will support a blood bank recruitment coordinator, who will work to collect clinical data on birth, growth, endocrine functions and feeding behavior in newly diagnosed patients with PWS.

Prader-Willi Syndrome (PWS) is a complex genetic disorder associated with varied clinical findings, neurocognitive delay, and endocrine abnormalities. Clinically, individuals with PWS progress along a path marked by different nutritional stages. In infancy, children with PWS have hypotonia, poor feeding, excessive daytime sleepiness, and...

: 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 disease.

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...

Many advances in recent years have added to our understanding of the genetic causes of PWS, including recognition of it as a disorder of genomic imprinting involving defective genes that normally only function after inheritance from the father. At least a dozen genes appear to contribute to the many clinical problems seen in PWS. Unfortunately the...

Early in infancy, babies with Prader-Willi syndrome (PWS) have no interest in feeding manifested by lack of crying for food and failure-to-thrive requiring assisted feeding with a G-tube, NG tube, or cross-cutting of bottle nipple (phase 1a). There is then a series of transition through five nutritional phases, ending in the classic PWS...

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....

Background: Hypogonadism (impaired sex hormone production) is a major feature of PWS, although the clinical expression is variable. Nevertheless, early onset of puberty has been seen in both sexes, and pregnancies have been documented in some PWS women. The causes of hypogonadism in PWS are heterogeneous, encompassing a spectrum which includes...

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...

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...

Hypogonadism (decreased production of testicular or ovarian hormones resulting in incomplete sexual development) is considered to be a cardinal feature of Prader-Willi syndrome, however, the clinical expression is variable. Most, but not all PWS males have unilateral or bilateral undescended testes. Arrested pubertal development leads to...

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...

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...

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...

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...

Prader-Willi Syndrome (PWS) is a condition characterized by growth hormone deficiency, hypogonadism, various behavioral disturbances, an insatiable hunger drive (hyperphagia) 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...

Genetic studies strongly indicate that the Prader-Willi syndrome is caused by the loss of small nucleolar RNAs (snoRNA). SnoRNAs are short RNAs that do not encode a protein. In most cases studied, snoRNAs help in the modification of other RNAs. However, the function of the snoRNAs missing in people with Prader-Willi syndrome is not clear. In...

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...

(Year 2 of this project)

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...

Despite years of study, we do not yet know the basis of Prader-Willi syndrome (PWS), either the roles of the genes defective in PWS or the basis of the clinical features. Many people think the hypothalamus, a small brain region controlling appetite and many endocrine functions is solely responsible, yet this may not be the single cause and using a...

This study examines the effect of growth hormone replacement therapy (GHRT) on physical and behavioral sexual maturation in males and females with Prader-Willi syndrome (PWS). Previously, sexual maturity among affected individuals has been largely ignored due in part to the assumed universality of underdeveloped/immature genitals, lack of sex...

This is Year 2 of a study to examine the effect of growth hormone replacement therapy (GHRT) on physical and behavioral sexual maturation in males and females with Prader-Willi syndrome (PWS). Previously, sexual maturity among affected individuals has been largely ignored due in part to the assumed universality of underdeveloped/immature genitals,...

An insatiable appetite (hyperphagia), 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...