Your One SMALL Step Funds at Work!
Summary of OSS funding to date, July 21, 2012
All proceeds from One SMALL Step events are applied to advance the Prader-Willi Research Plan, a result of the Prader-Willi Syndrome Research Strategy Workshop organized by the Foundation for Prader-Willi Research in 2009. During the Strategy Workshop, leading scientists in the fields of PWS and Obesity identified gaps in knowledge, prioritized basic clinical and research questions, and identified needed resources, technologies and training. A “Report to the Community” can be found at: http://fpwr.org/prader-willi-syndrome-research-strategy-workshop outlining the results of the workshop. Recomendations from the workshop were then used to formulate the PWS Research Plan, a research strategy jointly developed by FPWR and PWSA(USA).
2011 One SMALL Step contributions were applied towards Phase 1 of the PWS Research Plan.
Phase 1 funding of the PWS Research Plan focused on developing resources:
- PWS Molecular Resource Center - a website to promote the sharing of resources, models and information among scientists involved in PWS research
- Working Groups – teams of experts working to develop guidelines and recommendations to accelerate research: Obesity Clinical Trials Working Group, Mouse Models Working Group, Mental Health Working Group, and Biorepository/Registry Working Group. See below for details related to each working group. Working Group Details
- PWS iPS Cells – A research team led by Marc Lalande at the Connecticut Stem Cell Institute established pluripotent stem cells from individuals with PWS, establishing a critical resource for the PWS research community. The team’s goal is to use the cells to determine a list of genes that are specifically altered in PWS. iPS Cell Details
- Training - $50,000 has been set aside to train the “next generation” of PWS clinicians and scientists (funding has not yet been expended)
And addressing three research questions:
- What underlies the shift from failure to thrive to excessive hunger in PWS?
- Can the maternally silent genes in the PWS chromosome region be selectively reactivated?
- What are the cellular phenotype(s) of PWS?
Six research projects were funded addressing the 3 questions listed above:
- Q1 Nutritional Aspects of Prader-Willi syndrome and Childhood Obesity: Correlation of Plasma Orexin Levels with Nutritional Phases ($20,000)
- Q1 Development of leptin dysregulation in a mouse model of obesity in PWS ($148,600, 2 year grant)
- Q2 Small Molecular Screening and Therapeutic Potential for PWS ($50,000)
- Q2 Reactivation of maternally-silenced genes in PWS ($49,164)
- Q3 Use of Stem cell-derived neurons to identify the molecular basis of the PWS ($50,000)
- Q3 Pancreatic and neuro-endocrine cell secretory pathway deficits in PWS ($50,000)
In addition to these One SMALL Step funded projects, FPWR supported an additional project, using non-OSS funds: “Development of appetite-related neural circuits in a mouse model for PWS.”
Next Steps: One SMALL Step Funding for 2012-2013
Funding from our 2013 One SMALL Step events will continue to support working groups and the implementation of their recommendations as well as further developing Phase II of the PWS Research Plan. Additionally, funding has been designated for two grant cycles:
- Mental Illness in PWS, $300,000 Applications are due Sept 21, 2012. Details can be found here: http://www.fpwr.org/2012-mental-illness-pws-request-applications
Hyperphagia, $200,000 RFA will be announced following the Hyperphagia Conference in Oct 2012 with an estimated deadline of January/February 2013. http://www.hyperphagia.
One SMALL Step Funded Projects, RFA 1
Question 1: What underlies the shift from failure to thrive to excessive hunger in PWS?
Question 2: Can the maternally silent genes in the PWS chromosome region be selectively reactivated?
Question 3: What are the cellular phenotype(s) of PWS?
- Prioritize candidate drugs/therapies for evaluation in PWS
- Define the target population for the interventions, with consideration for age, genetic subtype, BMI, etc.
- Define surrogate endpoints, biomarkers, clinical endpoints
- Address how the unique development of obesity in PWS might influence intervention outcome
- Provide recommendations on trial design, recruitment, support needed to move clinical trials forward
- Consider ethical, clinical and behavioral issues specific to PWS, including risk for psychiatric complications
- Recommend a battery of assessments to characterize behavior, psychiatric illness and well-being in PWS.
- Promote PWS as a genetic model for studying mental illness
- Review the existing experience and prioritize interventions for evaluation in clinical trials.
- Define the target population for the interventions, with consideration for age, genetic subtype, etc.
- Provide recommendations on endpoints to determine efficacy, incorporation of potential markers that may be predictive of outcome (including imaging).
- Recommend standards for neurodevelopmental, behavioral, and metabolic assessments for PWS mice.
- Evaluate the feasibility/cost effectiveness of a PWS phenotyping consortium
- Provide recommendations on PWS-mouse model derived cell lines and tissues needed by the PWS research community; approaches to facilitate sharing.
- Evaluate non-PWS mouse models for their relevance to PWS
- Provide recommendations for additional animal models that are needed by the PWS research community, if any.
- Examine existing databases and repositories for PWS; determine how best to integrate
- Develop ‘common data elements’ for reporting clinical data
- Assess the need for a biorepository / tissue, evaluate avenues for development
- Develop guidelines for a governing board to address consent, outcomes reporting, ethical issues, ownership and oversight
- Lay the groundwork for efficient execution of clinical trials