Press Release (ePRNews.com) - WALNUT, Calif. - Mar 08, 2018 - The Foundation for Prader-Willi Research (FPWR) is pleased to share remarkable progress that has been made towards its mission of eliminating the challenges of Prader-Willi syndrome (PWS) and advancing therapeutic development. Two notable discoveries supported by FPWR have recently been published: 1) genetic activation of PWS genes in brain cells growing in a lab and 2) development of a novel mouse model that more closely recapitulates aspects of PWS. Both discoveries have been published in high-impact medical journals.
In the first study, stem cell researchers have used genetic methods to activate the silenced PWS genes – a first step towards genetic therapy for PWS. Using stem cells from an individual with PWS grown in the laboratory, UConn Health’s Maeva Langouet, a post-doctoral fellow; Marc Lalande, professor of Genetics and Genome Sciences; and their colleagues, deleted the gene ZNF274, which they previously showed was responsible for silencing genes in the PWS region of chromosome 15. They then coaxed the stem cells to grow into neurons and demonstrated that expression of the PWS genes was rescued, such that the cells had a normal gene expression pattern. Molecular analysis of the DNA following ZNF274 deletion also revealed details about how the PWS genes are silenced and activated, providing important clues that can be exploited for new therapeutic development. Although many additional steps are needed prior to testing this genetic approach in individuals with PWS, this study represents a critical step in demonstrating the feasibility of gene activation for PWS.
In a separate study, researchers at the University of Cambridge developed a new model of PWS that may accelerate therapeutic development. Excessive hunger (hyperphagia) and obesity are hallmark features of PWS, but no effective treatments have been found to date and progress has been hampered by the lack of a mouse model that reliably mimics these aspects of the disorder. Drs. Anthony Coll, Steve O’Rahilly, Giles Yeo and colleagues recently published a new mouse model of PWS in The Journal of Clinical Investigation. This model is notable in that it recapitulates the extreme hyperphagia and obesity of PWS for the first time. The authors plan to further refine this model for PWS, which could be used to test potential therapies for PWS hyperphagia.
“These discoveries provide new insights and tools that will accelerate PWS research and bring us closer to a time when our loved ones with PWS can live a healthy and full life,” said Theresa Strong, director of research programs at FPWR. “FPWR is excited to be supporting these and other innovative projects that are pushing the field forward.”
About Prader-Willi syndrome (PWS)
Prader-Willi syndrome is a rare, genetic disorder affecting approximately one in 15,000 people. PWS is a complex condition that impacts nearly every system in the body. The hallmark symptom of PWS is hyperphagia, an unrelenting appetite and extreme hunger. A person with PWS never feels full. There are currently no effective treatments to regulate appetite in PWS and individuals with PWS require a highly restricted environment to prevent life-threatening overeating and obesity. Additional associated problems include growth hormone deficiency, behavioral challenges, intellectual disability, anxiety, sleep disturbances and scoliosis. For many individuals with PWS, the elimination of hyperphagia would represent a critical advance, bringing new possibilities for an independent life.
About Foundation for Prader-Willi Research (FPWR)
FPWR is composed of thousands of parents, family members, researchers and others who are interested in addressing the many issues related to PWS, including childhood obesity, developmental delays, psychiatric disorders and autism spectrum disorders. The mission of FPWR is to eliminate the challenges of Prader-Willi syndrome through the advancement of research and therapeutic development. FPWR supports cutting-edge research studies around the world to advance the understanding of PWS and collaborates with research institutions, pharmaceutical companies and the FDA to advance new treatments that will help those with PWS. To date, FPWR has funded over $10 million in PWS research. For more information please visit https://www.fpwr.org/.
Maéva Langouët, Heather R Glatt-Deeley, Michael S Chung, Clémence M Dupont-Thibert, Elodie Mathieux, Erin C Banda, Christopher E Stoddard, Leann Crandall, Marc Lalande. Zinc finger protein 274 regulates imprinted expression of transcripts in Prader-Willi syndrome neurons. Human Molecular Genetics, 2018; 27 (3): 505 DOI: 10.1093/hmg/ddx420
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Foundation for Prader-Willi Research