Translational Research Programs

Creating Critical Knowledge

Genotype to Phenotype

To improve therapies for PWS, we need to better understand how the loss of the PWS genes leads to the characteristics of PWS and how genes outside the PWS region influence the severity of disease symptoms. Fundamental insights into the underlying basis of PWS symptoms will lead to breakthrough therapies and more personalized approaches to treating PWS.

Neurobiology of Hyperphagia and Mental Health PWS

Hyperphagia and mental health issues are two of the greatest challenges faced by individuals with PWS. Through the neurobiology of feeding behavior program we will improve our understanding of 1) the neurobiology of hyperphagia, 2) progression from failure to thrive to hyperphagia, 3) eating behavior drive, 4) energy balance/metabolism. Studying the neurobiology of mental health will provide a better understanding of the underlying basis for intellectual disability, behavior problems and mental illness in PWS.

Through the Neurobiology of PWS program, we will gain a better understanding of why people with PWS develop hyperphagia and struggle with intellectual disabilities, behavior problems, and mental illness. By understanding the changes in the brains of those with PWS, we can identify new targets for drug development and determine which treatments are most promisiing

Therapeutic Approaches for PWS

Genetic Therapy for PWS

Genetic therapy has the potential to address the root cause of PWS. Through our genetic therapy program, we will determine if genetic approaches can reverse the symptoms of PWS. For example, what will happen if we introduce a single activated PWS gene? Can we partially or completely reverse PWS symptoms through gene replacement or gene activation techniques?

The goal of this program will be to focus on overall feasibility of gene activation or replacement as a therapeutic strategy. This program requires a long-term investment, but has the potential to be life-changing for our loved ones with PWS.

Four complimentary approaches to gene activation are in development for PWS and currently supported by FPWR. These include small molecules (drugs), CRISPR technology, “artificial transcription factor’ technology and disruption of specialized proteins that silence the PWS genes on the maternal chromosome. Each of these projects is underway in pilot phases, and we will determine which one(s) have the most potential to move forward.

Pharmaceutical Therapy for PWS

This program will support the development and repurposing of pharmacological therapies to address the most severe symptoms of PWS. New drug development is long and costly. Repurposing of drugs can drastically reduce development time and skip many of the pre-clinical phases. We will leverage our limited resources to accelerate the drug development and repurposing processes by funding proof of concept studies and bridging critical gaps.

Clinical Care Research

We all agree that our loved ones living with PWS need improved treatments NOW. Clinical care research aims to alleviate the symptoms (such as behavioral problems, scoliosis, seizures, GI motility, central adrenal insufficiency, hypotonia, etc.) of PWS to improve quality of life. Through this program, we will characterize common PWS clinical complications and evaluate existing medicines and treatments to determine if they can be used to optimize the health and well-being of our loved ones with PWS in the near term.

Research Tools

A well-thought-out set of tools and infrastructure is critical to support PWS research and accelerate the work at hand. Such tools are typically not supported by other funding sources, so it is up to us, FPWR and the PWS community, to ensure these tools are developed. By providing critical tools that all researchers can use, we can leverage our funds and accelerate research across disciplines. FPWR is in a unique position to facilitate collaboration across stakeholders and provide research tools to the community, which will improve efficiency and accelerate the development of effective therapies for PWS.

Pre-Clinical Animal Network. Drug development is long and costly. To protect our investments, we need to be able to efficiently predict the safety and efficacy of drug candidates for PWS prior to sending them into clinical trials. The pre-clinical animal network, composed of expert model laboratories, will improve the predictive value of our PWS models, improve our ability to accurately predict drug safety and efficacy, and will serve as a pre-clinical drug screening platform. Learn more >>

New Animal Models. Disease models are critical for therapeutic development in order to test the safety and efficacy of candidate drugs. Based on the input of experts, we will develop the new animal models of PWS needed to advance therapeutic development. Learn more >>

PWS cellular network. Modeling PWS in a cell is critical for screening drugs in a high throughput fashion. We will develop a network of investigators to develop assays and cellular models of PWS for identifying new drugs, reposition existing drugs or discover new targets and pathways that can be used for investigating disease mechanisms as well as drug discovery. Learn more >>

PWS Clinical Trials Consortium. There are many opportunities and challenges for current and future clinical trials for treating hyperphagia in PWS. The PWS Clinical Trials Consortium is leveraging the expertise and perspective from industry, academia, governmental agencies, and patient organizations to address the scientific, technical, clinical, and regulatory needs for clinical trials. Learn more >>

Global PWS Registry. A comprehensive database of individuals with PWS will help us better understand the full spectrum of PWS characteristics, expedite the completion of clinical trials, and determine areas of needed research and treatments to improve the lives of those affected by PWS. Visit the Global PWS Registry >>

PWS Biobank. Biobanks are used to store biological samples, such as blood, urine, and cells, that can be made available to investigators as needed. We will evaluate the utility and feasibility of developing a PWS biobank and develop a standardized protocol for processing samples to improve data quality and reproducibility. FPWR has teamed with the Autism Brain net to establish a biobank for post-mortem brain tissue. Learn more >>

Data-Sharing Platform. A platform is needed to allow PWS investigators to readily share and analyze data and information. By pulling data from different sources, we will generate new information that will help us better understand the cause of PWS and develop new approaches to treat PWS.

PWS Clinical Trial Sites Network. Several clinical trials for PWS are either ongoing or planned for the near future. Considering the limited patient pool, there is a risk of inadequate recruitment and delay in the conduct of these trials. Currently, only a limited number of sites are involved in conducting the vast majority of PWS clinical trials across the country. This limits geographic coverage and results in a smaller patient pool from which to enroll for these trials. The goal of this program is to develop a network  of PWS Clinical Trial sites across the US and Canada to increase the number of sites and increase the number of participants. Do you have a possible PWS clinical trial site you could recommend? Submit your site recommendation here >>