The Foundation for Prader-Willi Research announces our first round of Research Awards in 2022 totaling $1,137,148. Our largest single round of funding in FPWR history, FPWR is excited to fund a robust group of 10 grants that encompass projects that will increase our foundational knowledge of PWS, explore new treatments for hyperphagia, and advance potential therapies into the clinic. FPWR is dedicated to supporting research that advances the understanding and treatment of Prader-Willi syndrome (PWS) and to that end, has awarded over $16,000,000 and funded 200+ research grants since 2003.
On a recent webinar, Dr. Theresa Strong provided an update on ongoing research activities, new outcomes from the FPWR grant program, and a brief description of each of the 10 funded grants, sharing why we're excited about them and what their potential long-term contribution could be.
FPWR PWS Research Grant Recipients, Spring 2022
- EFFECTS OF ULTRASOUND SENSORY NEUROMODULATION IN MULTIPLE MOUSE MODELS OF PRADER-WILLI SYNDROME. Christopher Puleo, PhD, General Electric Company, GE Research. Dr. Puleo and his team are investigating the use of peripheral ultrasound to modulate targets in the brain and impact energy balance and weight. They have strong preliminary data in several mouse/rat models of obesity and have performed early-stage clinical trials in healthy obese people. Here they will investigate mouse models of PWS as a first step in determining the relevance of this therapeutic approach to PWS. Learn more >>
- MC3R INHIBITION AS A THERAPEUTIC STRATEGY FOR TREATING HYPERPHAGIA IN PRADER-WILLI SYNDROME. Patrick Sweeney, PhD, University of Illinois. Dr. Sweeney has shown that the melanocortin 3 receptor (MC3R) is important in regulating food intake and has developed an antagonist of MC3R that inhibits feeding. Here he will test whether inhibition of MC3R decreases food intake in a mouse model of PWS. Learn more >>
- PREFRONTAL CORTEX MC4R NEURONS AS A TARGET FOR FEEDING AND COGNITIVE SYMPTOMS IN PWS. Rachel Ross, Albert Einstein College of Medicine. Dr. Ross will investigate how feeding behavior and cognitive flexibility are jointly regulated in the prefrontal cortex of the brain, in neurons expressing MC4R. This study may define a neuronal circuit to target therapeutically. Learn more >>
- WHERE AND WHEN DOES SNORD116 INTERACT WITH ITS MRNA TARGETS? Deborah Good, PhD, Virginia Tech. The Snord116 gene is critical in PWS, but its normal function is incompletely understood. Dr. Good will establish an atlas of where and when the SNORD116 RNA is expressed in the developing mouse brain and how it interacts with one of its putative target genes, Nhlh2, to gain insight into the underlying molecular basis of PWS. Learn more >>
- UNRAVELING THE MECHANISM OF PWS BY MOLECULAR DISSECTION OF DRIVER GENES IN HYPOTHALAMIC NEURON MODEL (YEAR 2). Derek Tai, PhD, University of Michigan. This young investigator developed PWS cell lines representing type 1 and 2 deletions and has grown them as 3-D brain organoids, recapitulating the hypothalamus, in a dish. He has applied cutting-edge technology to understand how PWS neurons differ from typical neurons and has generated data on gene expression changes. In year 2, he will expand the study to include assessment of energy/metabolism and electrophysiology to understand the underlying mechanism of disease in PWS. Learn more >>
- MAGEL2 ROLE IN ADAPTIVE STRESS RESPONSE: NEW INSIGHTS INTO MAGEL2 FUNCTION AND PATHOGENESIS OF PWS. Klementina Fon Tacer, DVM, PhD, Texas Tech University. Dr. Fon Tacer has been investigating the function of the MAGEL2 protein and believes it plays an important role in how cells adapt to stress. In this study, she will explore how cellular stress responses are altered when MAGEL2 is lost. Learn more >>
- HOW DOES THE EPIGENETIC REGULATOR SMCHD1 REGULATE THE PWS CLUSTER IN HUMANS? Marnie Blewitt, PhD, WEHI. Dr. Blewitt has shown that inhibiting SMCHD1 allows several important protein-coding genes in the PWS to be expressed, but the effect is incomplete. Here she will determine the chromosomal landscape in the PWS region on the maternal chromosome and evaluate how that landscape changes when SMCHD1 is missing, paving the way for more efficient maternal gene activation to treat PWS. Learn more >>
- INVESTIGATION OF THE ROLE OF FKBP5 TO INDUCE PWS PHENOTYPES IN A MAGEL2-NULL MOUSE MODEL. Hui Yu, University of Michigan. (Year 2). With previous FPWR funding, Dr. Yu used advanced, single-cell sequencing to characterize changes in hypothalamic cells in a PWS mouse model and identified activation of a gene important in stress response and energy metabolism, Fkbp5. Here she will test whether inhibiting Fkbp5 rescues deficits in a PWS mouse model. Learn more >>
- GENETIC DETERMINANTS OF BEHAVIORAL, PHYSICAL, AND PHYSIOLOGICAL CHARACTERISTICS OF PWS. Elena Bochukova, PhD, University of London. The variability in PWS symptoms might be due to variation in genes outside of the PWS critical region. In order to understand these genetic contributions to the severity and complexity of the disease, Dr. Bochukova will analyze the variations in the genetic makeup of 160 PWS participants, and see how those are related to the measured biochemical, metabolic, behavioral and physical characteristics of these patients. The goal of this analysis is to deepen our understanding of genetic contributions to the severity and complexity of PWS from genes outside the Prader-Willi critical region. This analysis has the potential to identify new targets for therapeutic intervention in PWS. Learn more >>
- IMPACT OF BRIGHT LIGHT THERAPY ON ALL-CAUSE EXCESSIVE DAYTIME SLEEPINESS IN PRADER-WILLI SYNDROME. Deepan Singh, MD, Maimonides Hospital, Brooklyn, NY. Individuals with PWS have disrupted circadian rhythm, which can impact mood, cognition, and metabolism, and recent FPWR-supported studies demonstrate that those with disrupted sleep are more likely to experience behavior challenges and mental health problems. Dr. Singh will be performing a clinical trial of bright light therapy in children (6-18 years old) with daytime sleepiness, and will evaluate its effects on sleepiness, behavior, and activity. Learn more >>
