Events

Financials

The Foundation for Prader- Willi Research is extremely conscientious with the donations entrusted to our care. In 2016, 81% of every dollar spent went directly to research programs. As our most dedicated friends and supporters, you make our work possible. Thank you for all that you do!

Funded Projects

FPWR has funded more than 125 research grants since 2003, investing $8.5 million into PWS research around the world.

1. SMALL MOLECULE ALLOSTERIC MODULATORS OF THE MELANOCORTIN-4 RECEPTOR FOR THE TREATMENT OF PRADER-WILLI SYNDROME. Roger Cone, University of Michigan ($81,000). There are 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.
2. PHYSIOLOGICAL AND GENETIC DETERMINANTS ON HYPERTHERMIA AND HYPERPHAGIA IN PWS. Valter Tucci, Ph.D., Italian Institute of Technology ($75,600). 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 play a crucial role in the pathophysiology of PWS symptoms, including sleep and obesity. They will use PWS mice that will be maintained under different temperature regimens and then analyzed for sleep changes, body weight, food intake and energy expenditure.
3. WAKE PROMOTING EFFECTS OF OXYTOCIN (YEAR 2). Thomas Scammell, M.D., Harvard Medical School ($108,000). 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 unknown. 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 help us understand impairments in the brain’s ability to control sleep and wakefulness in PWS, and provide potential targets for intervention.
4. HE MOLECULAR MECHANISM OF SNORD116 ACTION AND POSSIBLE SNORD116 SUBSTITUTION STRATEGIES. Stefan Stamm, Ph.D., University of Kentucky ($70,000). 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 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.
5. RECAPITULATING OBESITY AND HYPERPHAGIA IN NOVEL ADULT-ONSET MOUSE MODELS OF SNORD116 DELETION. Giles Yeo, Ph.D., University of Cambridge ($87,600). 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 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 therapeutic interventions for obesity and hyperphagia in PWS.
6. UNDERSTANDING MULTIPLE HORMONE SECRETION DEFICITS IN PRADER-WILLI SYNDROME. Robert Nicholls, Ph.D., University of Pittsburgh Medical Center ($108,000). 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 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.
7. GHRELIN: IS IT DETRIMENTAL, BENEFICIAL, OR INCONSEQUENTIAL IN PRADER-WILLI SYNDROME? (YEAR 2). Jeffrey Zigman, M.D., Ph.D., University of Texas Southwestern Medical Center ($108,000). 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 to 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.
8. IMPROVING SOCIAL FUNCTIONING IN PRADER- WILLI SYNDROME. Elisabeth Dykens, Ph.D., Vanderbilt University ($108,000). People with intellectual or developmental disabilities, including Prader-Willi syndrome, are at heightened risk for social exclusion and isolation. This underpins loneliness, depression and anxiety, and 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 to impact young adults with PWS.
9. PRECLINICAL STUDIES OF A NOVEL EPIGENETIC THERAPY FOR PRADER-WILLI SYNDROME. Yong-hui Jiang, M.D., Ph.D., Duke University ($108,000). Dr. Jiang has identified a drug that can activate the maternal PWS genes. This project will advance that drug towards human clinical trials, establishing the safety and efficacy of gene activation in mouse models.
10. REACTIVATION OF THE PWS LOCUS VIA DISRUPTION OF THE ZNF274 SILENCING COMPLEX (YEAR 2). Marc Lalande, Ph.D., University of Connecticut ($86,400). In year one of support, Dr. Lalande and his group characterized the role of a regulatory protein, ZNF274, in silencing the PWS region on the maternal chromosome, and demonstrated that disruption of ZNF274 causes reactivation of the PWS genes. Here, they will extend that work and evaluate advanced methods of disrupting ZNF274 to allow efficient reactivation of the maternally-derived PWS region genes. {Funded in partnership with PWSA-UK}
11. THE MAGEL2 PHENOTYPE IN COMPARISON TO CLASSIC PRADER-WILLI SYNDROME. Christian Schaaf, M.D., Ph.D., Baylor College of Medicine ($106,941). Loss of the PWS region gene MAGEL2 has recently been described by Dr. Schaaf and associated with many of the characteristics of PWS. Here, Dr. Schaaf will examine in detail the behavioral, cognitive, and endocrine characteristics of ten individuals with mutations in the MAGEL2 gene only in comparison to those with classic PWS to understand how MAGEL2 contributes to the PWS characteristics.
12. LOSS OF MAGEL2 AND HYPOTONIA IN PRADER-WILLI SYNDROME. Rachel Wevrick, Ph.D., University of Alberta ($84,387). Dr. Wevrick’s group has found that mice missing the PWS-region gene MAGEL2 have reduced strength, activity levels and endurance. In this study, they will examine interventions including diet, supplements and drugs to improve hypotonia and muscle strength and endurance. The goal is to identify interventions that can be readily used in the clinic. {Funded in partnership with FPWR-Canada}
13. MITOCHONDRIAL COMPLEX I DYSFUNCTION IN PRADER WILLI SYNDROME: A NEW THERAPEUTIC TARGET. Ingrid Tein, M.D., Hospital for Sick Children, Toronto ($108,000). Dr. Tein is an expert in energy metabolism and muscle fitness who is examining mitochondrial dysfunction in PWS. Her group will carefully study the effects of CoQ10 in adolescents with PWS, measuring effects on strength, endurance, and muscle function. This study should provide important guidance on the use of CoQ10 in PWS. {Funded in partnership with FPWR-Canada}
14. A POST-MORTEM STUDY OF VON ECONOMO NEURONS IN THE FRONTAL CORTEX OF BRAINS OF PERSONS WITH PWS. Patrick Hof, M.D., Mount Sinai ($75,600). Dr. Hof is an expert in neuroanatomy. He will study the structure and distribution of a type of neuron (von Economo neurons) that are critical for sensory awareness, social interaction, and problem solving. These neurons are disrupted in other disorders, such as autism, but have not yet been studied in PWS. {Funded in partnership with Prader-Willi France}
15. PREDICTORS OF PSYCHOSIS IN PRADER WILLI SYNDROME. Carrie Bearden, Ph.D., UCLA ($107,991). Dr. Bearden focuses on identifying the earliest (prodromal) phase in the onset of mental illness. Here, she will apply the lessons from other populations to better define the predictors of impending mental illness in PWS. They will evaluate an online assessment approach to determine the cognitive profiles of those most vulnerable to onset of mental illness. The ultimate goal of this study is early detection of those at highest risk to allow early intervention to prevent or mitigate psychotic illness.
16. PLASTIC TASTER: A SWITCHING TRAINING GAME FOR PEOPLE WITH PWS THAT ADAPTS TO INDIVIDUAL NEEDS (YEAR 2). Kate Woodcock, Ph.D., Queens University, Belfast ($86,400). Dr. Woodcock is interested in understanding the underlying triggers for temper tantrums in PWS, and has identified “task switching” as a significant challenge. This project aims to develop a software prototype directed at teaching and improving task switching in PWS. In year 2, development of the prototype will be extended to adapt to individual needs and tailored to encourage adoption of the improved task switching to everyday life.
17. EVIDENCE-BASED APPROACH TO DIETARY MANAGEMENT OF PWS. Mark Freemark, M.D., and Andrea Haqq, M.D. ($20,000). This supplement to a previous award will allow the investigators to complete a study of the effects of two different diets (low carbohydrate/high fat compared to high carbohydrate/low fat) on metabolism in children with PWS.
18. OXYTOCIN TREATMENT IN MAGEL2 DEFICIENT MICE (YEAR 2). Francois Muscatelli, Ph.D., INSERM ($86,450). Dr. Muscatelli will continue her work developing novel mouse models to investigate how early treatment of a PWS mouse with oxytocin results in improvements in feeding, cognition and social interaction. Using advanced genetic engineering, she will investigate the interaction of the PWS region gene, MAGEL2, and the oxytocin system, with the ultimate goal of informing human clinical intervention studies. {Funded in partnership with Prader-Willi France}