# Cardiac and Arteriolar Lesions in Fabry Disease and Dysautonomia

> **NIH NIH U54** · UNIVERSITY OF MINNESOTA · 2024 · $107,702

## Abstract

Abstract
Fabry disease, an uncommon disease caused by deficiency of lysosomal enzyme α-galactosidase A, leads to
intracellular accumulation of its substrates, mainly globotriaosylceramide (GL3), causing severe multi-organ
complications. Enzyme replacement therapy (ERT) is the current standard treatment for patients with Fabry
disease. However, some cells, including kidney podocytes (PC), cardiac myocytes (CM) and vascular smooth
muscle cells (VSMC), are relatively resistant to ERT, this creating residual risks in a substantial proportion of
ERT treated patients for serious complications, such as stroke, heart and renal failure. While cardiovascular
complications are the most common, and renal complications the next most common, cause of death in Fabry
disease, the pathophysiology of the lesions underlying these complications is poorly understood and requires
further studies. Such studies need access to large number of patients and biopsies and detailed clinical
information, these being common roadblocks in the study of rare diseases. The Lysosomal Disease Network
(LDN) has created a unique opportunity of networking among the investigators studying such rare diseases.
Using our extensive network of collaborators inside and outside of LDN as well as our own rich cardiac, renal,
and skin biopsy collections, we are extremely well poised to study the natural history and ERT treatment
outcomes of the key lesions of cardiovascular and renal complications of Fabry disease through novel
morphometric approaches that we have developed. These validated specific and quantitative approaches will
allow us to describe the relationships between these lesions and cardiac and renal function. We will also study
skin arteriolar VSMC including in patients with concomitant renal biopsies in order to determine if a less
invasive approach will provide vital organ information regarding these important cells in less accessible tissues.
In addition, we will study the effect of ERT on GL3 clearance from cardiac myocytes and cardiac, renal and
skin VSMC so as to determine factors influencing the effectiveness of ERT. These studies are highly likely to
provide reproducible and sensitive structural endpoints for future Fabry disease clinical trials exploring new
treatment approaches. In addition, we will assess tilt table variability of heart rate and blood pressure
response, as well as electrocardiographic (ECG) markers of ventricular depolarization/repolarization in order to
detect the presence and severity of dysautonomia in Fabry disease and, in pilot studies, to test whether these
dysautonomia and ECG parameters can predict the development of cardiac events/dysfunction in Fabry
patients. These unique cardiac and renal projects are highly likely to lead to new insights furthering our
understanding of Fabry disease and to new clinical trial strategies.

## Key facts

- **NIH application ID:** 10930045
- **Project number:** 5U54NS065768-15
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** S. Michael Mauer
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $107,702
- **Award type:** 5
- **Project period:** 2009-07-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10930045

## Citation

> US National Institutes of Health, RePORTER application 10930045, Cardiac and Arteriolar Lesions in Fabry Disease and Dysautonomia (5U54NS065768-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10930045. Licensed CC0.

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