Multi-omics research uncovers new therapeutic targets for Fabry disease

A comprehensive review is shedding new light on Fabry disease, a rare inherited disorder that can progressively damage multiple organs and significantly affect quality of life. The article highlights how advances in multi-omics technologies, including transcriptomics, proteomics, and metabolomics, are expanding understanding of the biological processes that drive organ injury and opening new possibilities for earlier diagnosis and more personalized treatment.

Fabry disease is caused by mutations in the GLA gene, resulting in reduced activity of the enzyme α-galactosidase A. This deficiency leads to the accumulation of metabolic substances within cells, triggering widespread damage throughout the body. Although current treatments can slow disease progression, many patients continue to experience complications affecting the kidneys, heart, nervous system, skin, eyes, ears, and reproductive organs.

The review emphasizes that organ injury in Fabry disease involves far more than the buildup of metabolic material alone. Emerging evidence points to a complex network of biological disturbances, including oxidative stress, inflammation, mitochondrial dysfunction, abnormal cellular signaling, fibrosis, and immune activation. These interconnected processes appear to play a critical role in the progression of tissue damage across multiple organ systems.

Particular attention is given to kidney disease, one of the most serious manifestations of Fabry disease. The review describes how injury to specialized kidney cells known as podocytes contributes to protein leakage, scarring, and eventual loss of kidney function. New findings also suggest that disrupted energy metabolism, ferroptosis, complement activation, and immune cell involvement may contribute to kidney damage.

The heart is another major target of the disease. Cardiac complications can include left ventricular hypertrophy, fibrosis, arrhythmias, and heart failure. The review highlights evidence linking cardiac injury to oxidative stress, impaired cellular energy production, altered lipid metabolism, and abnormal protein trafficking. These mechanisms may help explain why some patients continue to experience heart damage despite existing therapies.

Neurological complications are also explored, including stroke, chronic pain, sensory abnormalities, and autonomic dysfunction. The review describes how vascular injury, neuroinflammation, oxidative damage, and altered nerve signaling may contribute to both central and peripheral nervous system involvement.

Beyond improving understanding of disease mechanisms, multi-omics approaches are helping identify potential biomarkers and therapeutic targets that could support more precise patient management. The review also discusses advances in enzyme replacement therapy, chaperone therapy, gene therapy, and substrate reduction therapy, highlighting a rapidly evolving treatment landscape.