Registry biomarker study in RASopathy patients
Research type
Research Study
Full title
“A Registry Study to Characterize Genetic and Pathway Biomarkers in Noonan Syndrome and other RASopathy Patients“
IRAS ID
125207
Contact name
Bronwyn Kerr
Contact email
Sponsor organisation
Novartis Pharma AG
Research summary
This is a prospective, non-interventional biomarker study to characterise the genetic, genomic and signaling pathway perturbations of RASopathy syndromes.
RASopathy is a cluster of developmental syndromes that is caused by genetic mutations in the RAS/RAF/MEK/ERK signaling pathway. There are a number of related syndromes within this set of genetic syndromes (e.g. Noonan Syndrome, LEOPARD Syndrome, Costello Syndrome, CFC) all of which show specific mutations which then manifest into difficult and sometimes life threatening clinical symptoms.
With approximately 1% of babies affected each year, congenital heart diseases are the most common type of birth defect and the number one cause of birth-related deaths. Primary Hypertrophic Cardiomyopathy (HCM), which affects the cardiac muscle wall, is a common cause of mortality and morbidity in these patients. Patients with RASopathy syndromes often develop hypertrophic cardiomyopathy (thickening of the walls of the heart). Currently, treatment is focused on relief of symptoms (beta-blockers, calcium channel blockers and surgery, and toward sudden death prevention (amiodarone and implantable cardioverter defibrillator). However, these treatments are marginally effective and morbidity and mortality remain high.In a study in mice with a human Noonan syndrome mutation, the MEK inhibitor PD0325901 normalised the growth and defects in cardiac muscles. These data suggest that MAPK pathway inhibition may provide a new mechanism based approach in treating patients with RASopathy syndromes. However, little is known about the comparative MAPK pathway activity profiles of RASopathy syndromes and its relation to HCM. This study aims to profile the MEPK pathway inpatients with RASopathy syndromes and existing HCM.
Seventy subjects (20 from the United Kingdom), will be enrolled into this multi-centre study. Participants will be required to attend between 3-5 study visits over the course of a year: Screening visit, Baseline visit (Screening and Baseline can be conducted on the same day), 6-month, 12-month, end of study visit.REC name
North West - Haydock Research Ethics Committee
REC reference
13/NW/0319
Date of REC Opinion
11 Jun 2013
REC opinion
Further Information Favourable Opinion