We are pleased to announce the recipients of our second round of grants for 2024, totaling $1,681,781 in awards, as part of the Foundation for Prader-Willi Research’s (FPWR) ongoing commitment to advancing research in Prader-Willi syndrome (PWS) and Schaaf-Yang syndrome (SYS). These grants will support vital research efforts, providing new insights into PWS- and SYS-related topics and accelerating the development of potential therapies and interventions.
“We’re excited to support this outstanding set of research proposals, which will build critical knowledge of PWS-region genes, explore new approaches to treating PWS & SYS, and enhance our ability to care for individuals with PWS and SYS,” says Dr. Theresa Strong, Director of Research Programs.
Dr. Strong recently shared an update on ongoing research activities, highlighting promising outcomes from FPWR’s grant program. In the recorded presentation below, she provides an overview of the 12 newly funded projects, each of which is poised to make a significant impact in the field of PWS and SYS research.
FPWR PWS Research Grant Recipients, Fall 2024
- ELUCIDATING PHENOTYPIC DIFFERENCES BETWEEN PWS AND SYS: EXPLORING MAGEL2 FATE IN HUMAN NEURONS. Magdalena Laugsch, PhD, Heidelberg University Hospital ($162,000). Dr. Laugsch's group will examine the normal function of the MAGEL2 protein compared to MAGEL2 harboring SYS mutations, analyzing neuronal growth and function in the laboratory. Learn more in this video clip >>
- NOVEL FUNCTIONS AND TRANSLATION MECHANISMS INVOLVING A SNURF AND NEURAL-SPECIFIC SMN SPLICEOSOMAL PROTEIN. Joel McManus, PhD, Carnegie Mellon University ($161,998). One of the major genes in the PWS critical region, SNURF-SNRPN, is relatively understudied. Here, Dr. McManus will use cell models of human brain, pancreas, and heart to understand the function of the proteins that this gene produces. Learn more in this video clip >>
- EXPLORING THE ROLES OF SNORD115 AND SNORD116 GENES IN PERINATAL ADAPTATION. Jerome Cavaille, PhD, CNRS DR14 ($108,000). This project will evaluate therapeutic approaches to alleviate metabolic changes in the newborn period and determine whether these treatments impact the adult phenotype, using a new Snord115-116 knock-out model of PWS. Learn more in this video clip >>
- SIMILAR METABOLIC PATHWAYS ARE AFFECTED IN BOTH PRADER-WILLI SYNDROME AND CONGENITAL MYASTHENIC SYNDROME-22. John Creemers, PhD, Catholic University of Leuven ($108,000). Dr. Creemers has evidence that PWS has molecular similarities to another genetic disorder. CMS22. Here the lab will evaluate if the protein associated with CMS22 (PREPL) can rescue the PWS neonatal phenotype. Learn more in this video clip >>
- ENDOPLASMIC RETICULUM (ER) CHAPERONES IN PRADER-WILLI SYNDROME: THERAPY AND MECHANISMS. Robert Nicholls, PhD, University of Pittsburgh ($161,999). Dr. Nicholls has identified deficits in ER chaperone proteins in the pancreas as an important contributor to endocrine dysfunction in PWS. Here he will assess the ability of drugs that activate these chaperone proteins to rescue the newborn phenotype (ICdel mice). Learn more in this video clip >>
- GENETIC DETERMINANTS OF BEHAVIORAL PHYSICAL AND PHYSIOLOGICAL CHARACTERISTICS OF PWS (YEAR 2). Elena Bochukova, PhD, Queen Mary University of London ($137,160). This second year of funding expands Dr. Bochukova's work to understand how genetic variants outside the PWS region influence critical aspects of the phenotype. Learn more in this video clip >>
- CELLULAR AND MOLECULAR BASIS FOR OBESITY IN PWS (YEAR 2). Jeffrey Friedman, PhD, The Rockefeller University ($162,000). This renewal application builds on excellent work to date from the Friedman lab, which has identified a new subset of neurons in the hypothalamus and a novel gene that may be driving hyperphagia in PWS. They will explore how Magel2 impacts the function in these neurons and whether a pharmacological approach can impact the target gene and modify appetite. Learn more in this video clip >>
- REVEALING THE MOLECULAR ARCHITECTURE OF PWS THROUGH LARGE LANGUAGE MODELS FOR TARGETED DRUG REPURPOSING. Rohit Singh, PhD, Duke University ($107,144). Dr. Singh will apply artificial intelligence to PWS datasets to glean new information about pathways disrupted in PWS and possible targets for therapy. Learn more in this video clip >>
- EPIGENOME EDITING FOR STABLE REACTIVATION OF MATERNAL PWS GENES (YEAR 2). Charles Gersbach, PhD, Duke University ($162,000). Dr. Gersbach continues work examining advanced CRISPR tools to understand the regulation of the PWS region and optimize gene activation strategies. Learn more in this video clip >>
- AN INNOVATIVE NON-VIRAL DELIVERY OF CRISPR/DCAS9 EPIGENOME EDITING-BASED THERAPY FOR PRADER-WILLI SYNDROME. Xiaona Lu, PhD, Yale University School of Medicine ($162,000). Dr. Lu will use an innovative delivery system to achieve CRISPR gene activation in a new mouse model of PWS. Learn more in this video clip >>
- USING DESIGNER MILK EXOSOMES FOR RESTORING MAGEL2 EXPRESSION IN THE BRAINS OF MAGEL2 KNOCKOUT MICE. Janos Zempleni, PhD, University of Nebraska ($162,000). Exosomes are nonviral fragments of cells that can be used for the delivery of genes. Dr. Zempleni has developed targeted milk exosomes and will apply that approach to deliver a critical gene from the PWS region, Magel2, to a mouse model of PWS. Learn more in this video clip >>
- ANALYSIS OF DELAYED NEURAL DEVELOPMENT IN PWS DPSC NEURONS (YEAR 2). Larry Reiter, Tulane University ($87,480). Dr. Reiter has used stem cells derived from baby teeth to look at differences in how PWS neurons in a dish develop compared to typical neurons. He has found changes in circadian rhythm and timing of development. Year 2 work will focus on ‘rescuing’ these characteristics by delivering different PWS-region genes to the cells. Learn more in this video clip >>
