ERT for Fabry disease can limit blood vessel damage in kidneys
Treatment may protect vital organs by raising levels of vessel-repairing protein
Enzyme replacement therapy (ERT) may help limit damage to blood vessels in the kidneys of people with Fabry disease, a new study reports.
Specifically, the study found that people with Fabry who had been on ERT for longer had higher levels of VEGF-165b. This molecule is known to help repair specialized cells in the kidney that are essential for blood vessel integrity.
The study, “Urinary VEGF-A165b mRNA expression in Fabry Disease. Pilot study,” was published in NefrologÃa.
Fabry disease and kidney damage
Fabry is a rare genetic disorder caused by a deficiency of the enzyme alpha-galactosidase A (alpha-Gal A). Without a working version of this enzyme, specific fatty molecules accumulate to toxic levels inside cells, leading to symptoms that can affect the heart, kidneys, and nervous system. ERT is a type of treatment for Fabry that provides patients with a functional version of the missing enzyme to help reduce these harmful buildups and manage disease progression.
The kidneys, a pair of organs in the lower abdomen responsible for filtering blood and excreting urine, are often affected by Fabry disease. The kidneys are full of tiny blood vessels that filter blood, and Fabry can cause damage to these vessels.
VEGF-A165b is a molecule that can help protect small blood vessels. In studies of diabetic kidney disease, it showed a protective effect by helping restore podocytes, which are specialized cells in the kidney that wrap around tiny blood vessels inside filtering units called glomeruli.
Since Fabry patients often have damage in kidney blood vessels, scientists in Argentina hypothesized that VEGF-165b activity in the kidneys may be elevated in this population. To test this idea, the researchers analyzed urine samples from 24 people with Fabry disease and 24 healthy volunteers.
The scientists measured VEGF-165b messenger RNA (mRNA) levels in the urine samples. mRNA is an intermediary molecule made when genes are read to make protein. Since VEGF-165b mRNA is used to make VEGF-165b protein, higher mRNA levels indicate higher protein levels.
The scientists found that VEGF-165b mRNA levels tended to be higher in urine from Fabry patients, but the difference was not statistically significant (meaning it’s mathematically plausible that this difference is random chance). The researchers stressed that this was a relatively small study, noting that larger studies may be needed to find statistically meaningful results.
Nine of the Fabry patients were taking the ERT Fabrazyme (agalsidase beta). Statistical analyses of data from these patients revealed a significant correlation between time on ERT and levels of VEGF-165b mRNA. In other words, patients taking ERT longer tended to have higher VEGF-165b mRNA levels.
Since VEGF-165b is associated with blood vessel repair, the researchers speculated that this finding might reflect kidney vessel repair in Fabry patients who’ve been on long-term treatment. “Probably in patients with longer treatment time there is a decrease in [Fabry-related] damage,” the researchers wrote. The scientists stressed, however, that additional, larger studies are needed to validate these findings.
Fabrazyme is sold by Sanofi, which was not involved with this study.
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