The Foundation for Prader-Willi Research announces our first round of Research Awards in 2020 totaling $912,251. FPWR is dedicated to supporting research that advances the understanding and treatment of Prader-Willi syndrome (PWS) and to that end, has awarded over $14,000,000 to research since 2003.
On a recent webinar, Dr. Theresa Strong reviewed each of the 9 funded grants, sharing why we're excited about them and what their potential long term contribution could be. You can watch the full 60-minute webinar here or use the links below to watch short 2-minute segments on each specific project.
FPWR PWS Research Grant Recipients, Spring 2020
Long non-coding RNAs transcribed from Prader-Willi syndrome locus: key regulators of gene expression. Pawel Grzechnik, Univ Birmingham UK. Dr. Grzechnik’s lab is interested in uncovering the biological mechanisms underlying PWS. The deletion in the PWS locus affects the regulation of gene expression in neurons, but scientists are not exactly sure how this mechanism works. This current project is testing how coding and non-coding regions of the human genome are transcribed in cells lacking specific PWS-related non-coding RNAs, which will help to identify regulators of gene expression in PWS. Learn more >>
Novel Transcriptomic Signatures in Blood and Brain Predictive of Behavioral Issues in PWS. David Godler, Murdoch Children’s Research Institute. Dr. Godler’s lab is interested in identifying early predictors of autism and serious mental illness in PWS. In their preliminary data, they have found that inflammatory pathways linked to UBE3A (a key gene that regulates normal brain development and immune cell function) were affected differently in PWS caused by uniparental disomy (UPD), compared to deletion PWS. This study will extend that data, examining how UBE3A activity and the related immune cell inflammatory pathways affect behavioral issues in children and adolescents with PWS, comparing deletion and non-deletion PWS. Learn more >>
The role of the placenta in PWS: mapping the expression of PWS genes. Anthony Isles, Cardiff University. Dr. Isles and other researchers have shown that abnormal placental function can have profound consequences for brain and behavioral development in the offspring, and that abnormal signaling from the fetal placenta can also have consequences for maternal brain and behavior, which in turn may impact offspring neurodevelopment. This project examines the role of PWS genes in the placenta to understand how they contribute to brain development and behavior. As a first step, the research team will generate a detailed map of PWS gene expression in the placenta, as well as examine the structure and physiology of the placenta in a mouse model of PWS. Learn more >>
Identification of critical periods for the neurodevelopmental and behavioral effects of oxytocin (YEAR 2). Sebastien Bouret and Francoise Muscatelli, INSERM. The goal of the second year of this research project is to determine, using a preclinical mouse model of PWS, when do the maximal health and biological effects of oxytocin occur (birth, infancy, puberty, or adult life). The study also examines neurological mechanisms by which oxytocin treatment exerts its effects on feeding and behavior in PWS. This research project is important to optimizing oxytocin as a therapeutic strategy to ameliorate feeding, cognitive, and behavioral symptoms in PWS. Learn more >>
The functional development of hunger neurons in Prader-Willi Syndrome (year 2). Marcelo Dietrich, Yale University. Dr. Dietrich’s lab has been working on “hunger” neurons, Agrp neurons, that are contained in the hypothalamus in animal brains. They have found that PWS-related genes, particularly Magel2, are enriched in Agrp neurons. In the second year of funding for this study, they will use a mouse model that is missing Magel2 to look at the function of the Agrp neurons from breastfeeding to adulthood, which will help identify the pathophysiology of PWS. Learn more >>
Gene Therapy of Obesity in Prader-Willi Syndrome by an Autoregulatory BDNF Vector. Lei Cao, The Ohio State University. Hyperphagia and the associated metabolic dysregulation is one of the greatest challenges that individuals with PWS and their families face on a daily basis. Dr. Cao has developed a gene therapy that targets the metabolic roots of PWS within the brain’s center for energy regulation. Their group has developed an approach using a single dose of a gene whose deficiency is associated with human obesity (Brain-derived neurotrophic factor, or BDNF). This gene therapy is highly effective in animal models of obesity but has not yet been tested in a PWS animal model. Here, Dr. Cao and team will assess this perform novel gene therapy approach for metabolic dysregulation in a PWS mouse model. Learn more >>
Precise epigenome editing as a novel therapeutic opportunity for Prader-Willi syndrome. Claudio Mussolino, University of Freiburg. Dr. Mussolino and his team will use a novel approach to activate the maternal genes in the PWS regions. They are developing ‘designer epigenome modifiers’ (A-DEMs), to target key elements of the PWS-critical region on chromosome 15. This approach may allow more specific activation of genes in the PWS region of chromosome 15 for genetic therapy. They will test the approach in the lab, using cells from individuals with PWS. Learn more >>
Engineering epigenome editing tools for sustained reactivation of maternal PWS genes. Nahid Iglesias, Duke University. Dr. Iglesias has been working on potential genetic therapies for PWS and has shown that ‘epigenome editing’ can reactivate the maternal genes in the PWS region in human cells. The current study will focus on determining the molecular requirements to permanently reactivate the maternal genes in the PWS region, so that gene expression is maintained long-term in the cells. Learn more >>
Assessment of epigenetic driven circadian rhythm defects in neurons from individuals with PWS (Year 2). Larry Reiter, Univ Tennessee HSC. Dr. Reiter’s lab looks at stem cell lines from the teeth of PWS subjects to look at the sleep/wake cycle, called the circadian rhythm. People with PWS have a hard time with regulating this cycle. This project will use these stem cell lines to look at the PWS circadian rhythm patterns, as well as changes in DNA that are known to happen at different times during the day and night. Learn more >>
