Researchers are making progress every day toward FPWR's mission of eliminating the challenges of PWS and advancing therapeutic development. When their discoveries are published, that's an exciting moment for our community! So far in 2018, two notable discoveries supported by FPWR have been published:
- Genetic activation of PWS genes in brain cells growing in a lab
- Development of a novel mouse model that more closely recapitulates aspects of PWS
Both discoveries have been published in high-impact medical journals.
Genetic Methods to Activate Silenced PWS Genes
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 testing this genetic approach in individuals with PWS, this study represents a critical step in demonstrating the feasibility of gene activation for PWS.
Recapitulating Extreme Hyperphagia and Obesity
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.
FPWR's Director of Research Programs, Theresa Strong, put it well: “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. FPWR is excited to be supporting these and other innovative projects that are pushing the field forward.”