The Foundation for Prader-Willi Research (FPWR), in collaboration with FPWR-Canada and FPWR-UK, is thrilled to announce our second round of PWS research recipients for 2016! Eight outstanding projects were selected for funding, totaling $746,200 in support. These projects address a variety of topics important in PWS, including social functioning, hormone regulation, oxytocin and gene regulation.
Since 2003, FPWR has invested in 126 research projects. Our latest round of grants brings FPWR's total grant investment to over $8.25M!
"We're excited to be supporting an extremely strong group of research projects that will continue to advance our understanding of PWS, and lead to new treatments," said Theresa Strong, Director of Research Programs.
"We are proud to once again be able to support such a well rounded group of investigators," said Susan Hedstrom, Executive Director of FPWR. "FPWR is focused on funding research that will lead to treatments for PWS. The FPWR grant program to date has been fundamental to our efforts and we greatly appreciate the dedication of our supporters around the world who make this program possible."
Details on these projects as well as an exciting breakthrough will be shared on our upcoming webinar Wednesday, December 14th.
IMPROVING SOCIAL FUNCTIONING IN PRADER-WILLI SYNDROME Elisabeth Dykens, PhD, Vanderbilt University. People with intellectual or developmental disabilities, including Prader-Willi syndrome (PWS), are at heightened risk for social exclusion and isolation. This underpins loneliness, depression and anxiety, contributes to poor health and reduced longevity. This project will recruit 50 young adults with PWS into an intensive, 10-week group intervention aimed at improving social skills, perceptions and thinking, to help manage anxiety, depression, mental health problems, relationships with family, friends, and caretakers. The goal is to develop a program that can be extended and implemented to impact young adults with PWS.
UNDERSTANDING MULTIPLE HORMONE SECRETION DEFICITS IN PRADER-WILLI SYNDROME Robert Nicholls, PhD, University of Pittsburgh Medical Center. 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 new cell culture model system to study how PWS genes regulate hormone production and release. This study will advance our understanding of PWS at the cellular level, and may provide a platform that can be used for high throughput screening of small molecule therapies for PWS.
WAKE PROMOTING EFFECTS OF OXYTOCIN (year 2) Thomas Scammell, MD, Harvard Medical School. Caregivers, physicians and patients with PWS report that daytime sleepiness in PWS significantly disrupts daily life. However, the underlying cause of excessive daytime sleepiness in PWS is not well understood. Dr. Scammell’s group is exploring the contribution of reduced neuronal function in the hypothalamus region of the brain, specifically, oxytocin/orexin signaling. Using a photoactivation technique that specifically targets and activates certain subsets of neurons, this project will improve our understanding of how hypothalamic dysfunction impairs sleep and wakefulness in PWS, and provide potential targets for intervention.
THE MOLECULAR MECHANISM OF SNORD116 ACTION AND POSSIBLE SNORD116 SUBSTITUTION STRATEGIES Stefan Stamm, PhD, University of Kentucky. The loss of the snoRNA, SNORD116, plays a central role in the development of PWS, but 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 indicate that SNORD116 regulates a number of other RNAs. Here, they will define the genes that SNORD116 targets, potentially establishing new therapeutic targets, and explore approaches to replace SNORD116 function.
RECAPITULATING OBESITY AND HYPERPHAGIA IN NOVEL ADULT-ONSET MOUSE MODELS OF SNORD116 DELETION Giles Yeo, PhD, University of Cambridge. 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 preliminary studies, Dr. Yeo’s group has shown that if Snord116 is deleted in adult mice, a percentage of them do display the hallmark PWS features of obesity and hyperphagia. Studying this novel model in detail will help us understand SNORD116 function and also provide a new model for testing drugs for obesity and hyperphagia in PWS.
GHRELIN: IS IT DETRIMENTAL, BENEFICIAL, OR INCONSEQUENTIAL IN PRADER-WILLI SYNDROME? (Year 2) Jeffrey Zigman, MD, PhD, University of Texas Southwestern Medical Center. 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 food-seeking behaviors and obesity. Clarifying the role of ghrelin is a critical step for future therapies designed to target the ghrelin system in PWS.
PHYSIOLOGICAL AND GENETIC DETERMINANTS ON HYPERTHERMIA AND HYPERPHAGIA IN PWS Valter Tucci, PhD, Italian Institute of Technology. Dr. Tucci’s group has shown that mice with the SNORD116 deletion have sleep abnormalities and increased body temperature. They hypothesize that environmental temperature may be important in modulating PWS symptoms including sleep and obesity. They will maintain PWS mice under different temperature regimens and then analyze them for changes in sleep, body weight, food intake and energy expenditure.
SMALL MOLECULE ALLOSTERIC MODULATORS OF THE MELANOCOTIN-4 RECEPTOR FOR THE TREATMENT OF PRADER-WILLI SYNDROME Roger Cone, PhD, University of Michigan. 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 evaluated for PWS-associated hyperphagia.