Urine-derived Cells Are a Potential Diagnostic Tool for Fabry Disease, Researchers Say

Catarina Silva, MSc avatar

by Catarina Silva, MSc |

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urine-derived cells, Fabry diagnostic tool

Urine-derived cells from patients with Fabry disease are a promising diagnostic tool and an adequate cellular model to study the disease, according to German researchers.

Their study, “Urine-derived cells: a promising diagnostic tool in Fabry disease patients,” was published in Scientific Reports.

Fabry disease is caused by mutations in the GLA gene, which results in impaired activity of the alpha-Gal A enzyme.

This enzyme normally breaks down a type of fat called globotriaosylceramide (Gb3) in lysosomes, small vesicles that serve as the cells’ digestive system, leading to the accumulation of the fatty substance in tissues and cells — mainly those in the kidneys, heart, and central nervous system.

“To date, research has focused on the development of new biomarkers for diagnosis, but also for monitoring disease course and treatment efficacy. Nevertheless, the portfolio of routine biomarkers and disease models is still very limited,” researchers wrote.

Studies on genetic diseases affecting the kidney have shown that urine-derived cell cultures can be a noninvasive source of several cell types that mimic the disorders’ biological mechanisms.

“Patient-derived cells mark a step closer to the actual human pathology, as these cells carry the disease-causing mutation,” researchers wrote.

University Hospital of Cologne researchers in Germany explored the potential of primary urine cells — cells isolated from fresh urine samples and grown in a laboratory dish, as a Fabry disease diagnostic and disease progression assessment tool.

Urine-derived cells from seven Fabry patients (two females and five males) with distinct mutations in the GLA gene were grown in the lab and compared to cells from gender-matched healthy controls. The cultured cells modeled the type of cells (called epithelium) that line the inner structure of the kidneys.

A significant decrease in alpha-Gal A activity was observed in all Fabry patients’ derived cells. Specifically, three male samples had no alpha-Gal A activity whatsoever, while the two female patients exhibited low enzymatic activity.

Researchers also characterized protein content in four male samples. A total of 3,646 proteins were quantified and a strong decrease of α-Gal A expression in patient samples was observed when compared to healthy controls.

These patients also had an increased level of proteins connected to lysosomal function and production along with protein alterations linked to defective lysosomal biology.

“We present for the first time the potential of urine-derived cells for diagnosis and pathophysiologic evaluation in patients with Fabry disease. These cultured cells provide a model to investigate the [mechanisms] underlying Fabry disease and hold the potential of monitoring therapeutic efficacy,” researchers wrote.

Importantly, protein data obtained in this study from patient-derived urinary cells may be used as a first step to evaluate prognostic markers detectable in patient urine.

“In the context of personalized medicine, primary urine-derived cells could be exposed to different types of compounds or even gene-editing strategies to test their therapeutic capacity,” the researchers wrote.