We are pleased to announce the recipients of the second round of grants for 2023, totaling $1,000,000 in awards, as part of the Foundation for Prader-Willi Research's (FPWR) ongoing commitment to advancing research in Prader-Willi (PWS) and Schaaf-Yang (SYS) syndromes. These grants support critical investigations into PWS and SYS-related topics, providing valuable insights and driving the development of potential therapies and interventions.
Dr. Theresa Strong recently provided an update on ongoing research activities, new outcomes from the FPWR grant program, and a brief description of each of our 8 newly funded projects in the recorded presentation below.
FPWR PWS Research Grant Recipients, Fall 2023
- THE EFFECT OF GROWTH HORMONE TREATMENT ON PREMATURE AGING AND QUALITY OF LIFE IN ADULTS WITH PWS. Laura de Graaff, MD, PhD, Erasmus University Medical Center ($140,110). In PWS individuals aged 40 and up, quality of life (QoL) seems to be mainly impaired by premature aging, and premature aging in PWS seems less prominent in adults treated with growth hormone (GH). This project will investigate whether GH indeed slows down premature aging in PWS, by using a large group of older adults in the Netherlands that have never before received GH treatment. In this project, we want to investigate aging at both the clinical and cellular levels, including mobility, muscle strength, memory tasks, and cellular and DNA aging. This will increase understanding of the physical and cellular processes that cause premature aging in PWS, and if successful, make the case that GH should be a treatment for adults with PWS worldwide.
- INVESTIGATING THE ROLE OF SNORD116 IN RIBOSOME BIOLOGY. Amanda Whipple, PhD, Harvard University ($161,999). Through previous work using a new optimized method, Dr. Whipple discovered that Snord116, a driver of PWS, directly interacts with ribosomes, the machinery that produces proteins in the cell in mouse neurons. In this funded project, they will apply their optimized method to human neurons to ask if the interaction between SNORD116 and ribosomes is similar in humans. Then they will use advanced approaches to determine the effect that genetic deletion of Snord116 has on the proteins produced in mouse and human neurons.
- TRANSCRIPTOME-WIDE IDENTIFICATION AND FUNCTIONAL ANNOTATION OF PWS-ENCODED SNORD TARGETS. Chuan He, PhD, The University of Chicago ($162,000). The SNORD genes are known to be very important in PWS, but there is a lack of appropriate tools to study the target and function of these genes. Dr. He and his team have developed two new methods that can map the targets of the SNORD genes. They will apply these new methods to mouse models and human cell lines with a deficiency in PWS-encoded SNORDs to better understand the function of the SNORD genes and help us understand how the loss of these genes leads to the characteristics of PWS.
- EMERGENCY DEPARTMENT AND INPATIENT CARE OF INDIVIDUALS WITH PWS. James Luccarelli, MD, Massachusetts General Hospital ($98,029). Understanding the greatest clinical challenges is important in PWS, but there are individuals with PWS who are not participating in registry studies or surveys. Insurance claims data can be used to identify most people with PWS receiving care in the US. This project will analyze a vast database of claims from emergency departments and hospitals for information about the healthcare problems encountered by individuals with PWS in 2021. This study will be able to identify unique clinical challenges for PWS patients, explore mortality in people with PWS, and examine causes of death and clinical factors (including obesity) that may contribute to mortality. This will highlight the greatest areas of need in the ongoing treatment of PWS.
- THE ROLE OF OXYTOCIN RECEPTOR-EXPRESSING ASTROCYTES IN PRADER- WILLI AND SCHAAF-YANG SYNDROMES (YEAR 2). Christian Schaaf, MD, PhD, Heidelberg University ($162,000). Dr. Schaaf’s previous research showed that the ‘support cells’ in the brain (astrocytes) express receptors for oxytocin, are critically involved in the modulation of social behavior and anxiety and that there are differences in both the number and anatomical location of these astrocytes in healthy mice compared to a PWS mouse model. In this second year of funding, the team extended their studies to investigate whether these astrocytes contribute to abnormal behavior in PWS mice and whether these cells could be a valid target for therapeutic interventions. This study will provide novel insights into how impaired oxytocin signaling affects behavior in PWS, laying the foundation for potential therapies targeting astrocytes.
- EVALUATING DIRECT PLAY INTERVENTION FOR PRESCHOOLERS AND LONG-TERM FOLLOW-UP OF THE PRETEND PROGRAM. Anastasia Dimitropoulos, PhD, Case Western Reserve University ($132,558). The PRETEND program, developed by Dr. Dimitropoulos and her team, has been shown to improve aspects of social, emotional, and cognitive functioning in preschool and school-age children with PWS. The purpose of this funded project is to make the PRETEND Program available to more families by establishing a platform to train interventionists to use this program for broader dissemination. This project will also aim to improve the program for preschool children by adapting the protocol for in-person intervention and will explore the long-term effects of the program.
- WEARABLE DEVICE USE FOR HEART RATE VARIABILITY MEASUREMENT FOR OBJECTIVE ASSESSMENT OF HYPERPHAGIA. Ann O. Scheimann, MD, Johns Hopkins University School of Medicine ($71,548). Directly measured, objective outcomes are needed for Prader-Willi Syndrome (PWS) clinical trials for accurate assessment of treatment efficacy. We will conduct in-person focus groups of primary caregivers of children between 8-17 years with PWS to review potential options for wearable devices and options for daily diaries/data entry and use this data to study a wearable device within the natural patient environment. The first and second phases of the study will provide critical information about the feasibility of using emerging technology to assess heart rate variability (HRV) as an objective marker of behaviors in PWS such as outbursts, food seeking, and anxiety-related behaviors.
- USING FUNCTIONAL NEAR-INFRARED SPECTROSCOPY TO IDENTIFY BIOMARKERS OF SKIN-PICKING BEHAVIOR IN PWS. Scott Hall, PhD, Stanford University ($162,000). In previous research, Dr. Hall has found that altered internal bodily cues (interoceptive processes), such as pain, itch, and sensual touch, may be involved in skin-picking behavior in PWS. Here, he will employ a sophisticated brain imaging method called functional near-infrared spectroscopy (fNIRS), which allows brain activity to be measured under more naturalistic settings, to examine which regions of the brain are activated before, during, and after the occurrence of skin-picking behavior.