Social Outcomes in Adults with RASopathies: The SOAR Study

Awardee: Jonathan Payne

Institution: Murdoch Children's Research Institute

Grant Amount: $60,755.00

Funding Period: February 1, 2024 - January 31, 2025

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Summary:

Psychosocial difficulties and increased mental ill-health have been described in some RASopathies, however the literature lacks a systemic account of these difficulties, especially in adulthood. Understanding the nature, severity and impact of mental health and psychosocial adversity in adults with a RASopathy will be critical to inform clinical practice and to guide intervention strategies. The overall goal of the SOAR study is to take a holistic approach to evaluating a broad road range of psychosocial outcomes in adults with a RASopathy, including mental health, social integration, quality of life and daily living skills. We will also examine how these outcomes relate to demographic and personal variables such as employment, housing arrangements, family composition, and health status. SOAR will be a survey-based study and include over 300 adults with a RASopathy across Australia and the UK. By comprehensively characterizing the psychosocial outcomes in adults with RASopathies, this project will help shape clinical services and management of individuals with RASopathies.

The central conducting lymphatic system in patients with the Rasopathies Noonan Syndrome and CardioFacioCutaneous Syndrome with and without lymphatic disease

Awardee: Jos M Draaisma

Institution: Radboud University Medical Center

Grant Amount: $60,100.00

Funding Period: February 1, 2023 - January 31, 2024

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Summary:

To get a better insight into the central lymphatic system in adult volunteers with Noonan Syndrome (NS) and CardioFacioCutaneous (CFC) Syndrome without clinical symptoms or signs of lymphatic disease compared to healthy adult volunteers without disease and NS and CFC patients with severe lymphatic disease. This to enable therapy with MEK-inhibitors or lymphovenous anastomosis. The Dutch Noonan Syndrome Foundation participates in this study.

Discovery of new therapies for hypertrophic cardiomyopathy in RASopathies using an innovative hiPSC-based high-throughput drug screening platform

Awardee: Fabrice Jaffré

Institution: Weill Cornell Medical College

Grant Amount: $75,431

Funding Period: February 1, 2022 - January 31, 2023

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Summary:

Children with RASopathies often present with severe cardiomyopathies and have a 22% mortality rate by the end of the first year of life. Currently, no specific treatment exists for RASopathy children with hypertrophic cardiomyopathy, therefore there is an urgent need to identify novel therapeutic strategies. The overall goal of this proposal is to uncover innovative therapeutic approaches using human induced pluripotent stem cell-derived cardiomyocytes as a RASopathy disease model and as innovative human 2D and 3D high-throughput drug screening platforms. Completion of this proposal will identify therapeutic molecules for RASopathy children with hypertrophic cardiomyopathy at an unparalleled speed.

Understanding RASopathies to better inform diagnosis and treatment.

Awardee: Vanessa Fear

Institution: The University of Western Australia

Award Amount: $69,885

Funding Period: February 1, 2021 - January 31, 2022

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Summary:

The RASopathies are a set of syndromes that include cardiofaciocutaneous (CFC) Syndrome, Noonan Syndrome, Noonan Syndrome with lentigines, and Costello Syndrome.  The syndromes are characterised by overlapping disease phenotype and there is a need to distinguish the different RASopathies in order to facilitate accurate patient diagnosis and identify better treatments. In this study we compare changes in patient DNA (genetic variants) that are causative of CFC and Noonan Syndrome. Further, we investigate a potential disease causing patient genetic variant to determine if they have CFC or Noonan Syndrome. The study harnesses gene editing technology to introduce genetic variants into stem cells, which are then matured into nerve cells. The nerve cell maturation process is monitored to identify syndrome-specific changes to inform syndrome classification in the patient, and to provide a better understanding of both CFC and Noonan Syndrome.

MEK inhibition for RASopathy associated hypertrophic cardiomyopathy

Awardee: Gregor Andelfinger

Institution: CHU Sainte Justine Research Center, Université de Montréal

Award Amount: $59,220

Advancing A Novel Therapeutic Lead for RASopathies

Awardee: Bruce Gelb

Institution: Icahn School of Medicine at Mount Sinai

Award Amount: $74,830

Funding Period: February 1, 2019 - January 31, 2020

Targeting Endolysosomal Proteins to Treat RASopathies

Awardee: Kartik Venkatachalam

Institution: McGovern Medical School, University of Texas Health Science Center at Houston

Award Amount: $47,189

Funding Period: January 1, 2018 - December 31, 2018

Are Raf dimers targets for therapeutic intervention in RASopathies?

Awardee: Philip Stork

Institution: Oregon Health & Sciences University

Award Amount: $44,000

Funding Period: January 1, 2017 - December 31, 2017

Pain in RASopathies: new investigative techniques and treatments

Awardee: Giuseppe Zampino

Institution: Università Cattolica Sacro Cuore

Award Amount: $53,000

Funding Period: January 1, 2016 - December 31, 2016

Delineating the cause of gastrointestinal abnormalities in RASopathy disorders using human inducible pluripotent stem cells (iPSCs)

Awardee: Maria Kontaridis

Institution: Beth Israel Deaconess Medical Center/Harvard Medical School

Award Amount: $65,000

Funding Period: January 1, 2015 - December 31, 2015