Safe People
Lead applicant organisation name	University Hospitals Birmingham

Safe Projects
Project title	The STRIDE study: Surrogate biomarkers informing Treatment, Risk prediction and Identification of cardiac Dysfunction for Early Fabry management
Lay summary	Fabry disease is a multi-system, inherited disease that is due to decreased activity of an intracellular enzyme called alpha-galactosidase A . Lack of this enzyme causes build-up of the substrate, that include glycosphingolipids and globotriaosylceramide GL-3, that the enzyme usually breaks down (Bokhari, et al., 2022). Build up causes progressive cell dysfunction in multiple organs, begins in infancy and progresses until death. In the heart, this ultimately causes thickening (left ventricular hypertrophy), heart failure, and abnormal heart rhythms (ventricular tachycardia and fibrillation). Although treatments are available, evidence for their effect has been based on their impact on declining kidney function. The evidence that treatments improve the heart is limited but suggests these are more effective if given early and do not work when heart disease is advanced. Finding proof that early treatment helps is critical for patients because they have a shorter life expectancy than the general population, are 8 times more likely to die of heart disease than the general population, and about 5 times more likely to die of heart than kidney causes. While there some measures of heart decline have been published, these usually look at changes over years and are things that do not have a direct impact on how the patient feels, e.g. heart thickening (Pieroni, et al., 2022). We found that patients have a very early reduction in their physical fitness, that tracks over time with the changes in heart size, thickness and function (Roy, et al, 2025). We want to use anonymised patient data collected retrospectively through the clinical service, in partnership with a group that specialises in analysis to explore relationships between patient exercise capacity and their disease history. Our plan is then to explore whether day-to-day activity could be used as a surrogate measure for the detailed assessments in clinic, for use in a future trial of early therapy.
Public benefit statement	This project will generate insight into the long-term progression of Fabry-related heart disease, taking into account full clinical characterisation of the patient group over time, including multiple different markers of cardiac structure and function. The findings will: 1. Develop a multiparametric measure of progression and outcome over time. 2. Assess association with exercise capacity at early stage disease. 3. Support the development of new strategies to track patient activity as a marker of early cardiac involvement, that reflect underlying changes on complex imaging. The ultimate aim would be a home-based marker of involvement that can be tracked over time, and responds to intervention. This will improve risk stratification and personalized management of Fabry patients. The ultimate aim is to provide evidence to regulatory bodies regarding a valid, reliable patient-facing endpoint for clinical trials.
Latest approval date

Safe Data
Dataset(s) name	PATHWAY Research Data Hub: PWY040 dataset

Safe Setting
Access type	Data Licence Agreement between the collaborating organisations using secure and controlled data analysis environments.

Safe Outputs
Link	Not yet Published