Long-term ERT normalizes Fabry inflammation, oxidative stress
Study finds treatment over time produces sustained benefits
Long-term enzyme replacement therapy (ERT) normalizes markers of inflammation and oxidative stress in adults with Fabry disease, a study found.
“These findings lead us to believe that long-term ERT can improve the redox status and protect these individuals against oxidative … stress, as well as the inflammatory process,” researchers wrote in the study, “Long-term enzyme replacement therapy in Fabry patients protects against oxidative and inflammatory process,” which was published in Naunyn-Schmiedeberg’s Archives of Pharmacology.
Fabry is a rare, inherited condition marked by the toxic buildup of a fatty substance called globotriaosylceramide (Gb3) in the body’s cells, disrupting organ function, especially the kidneys and heart. It’s caused by mutations that lead to faulty or missing alpha-Gal A, an enzyme that breaks down Gb3.
In ERT, the standard Fabry treatment, a lab-made version of the alpha-Gal A enzyme is infused directly into the bloodstream. This helps the body break down Gb3, easing symptoms and delaying potentially life-threatening disease complications. Fabrazyme (agalsidase beta) and Elfabrio (pegunigalsidase alfa-iwxj) are two ERTs currently approved in the U.S.
Because Gb3 deposition also promotes a pro-inflammatory state in some patients, scientists in Brazil assessed the effects of ERT on inflammation and oxidative stress, a type of cell damage that occurs when reactive oxygen species outweigh the body’s antioxidant defenses.
Assessing for proteins
The team collected blood and urine samples from eight men and nine women with Fabry, while on ERT, and 17 healthy men and women who served as controls. The mean ERT treatment was 12.14 years for Fabry men and 7.75 years for women.
Blood was assessed for levels of pro- and anti-inflammatory immune signaling proteins (cytokines) and inflammation-related gene activity. Three oxidative stress markers were also measured.
Tests showed that the mean levels of all cytokines tested, including TNF-alpha, interleukin-6, IL-1-beta (pro-inflammatory), and IL-10 (anti-inflammatory), were significantly lower in men with Fabry than those of controls. Women with Fabry and controls had similar cytokine levels.
“The long-term treatment with ERT in men may be related to a decrease in the pro-inflammatory modulation (via cytokines) in these patients,” the researchers wrote.
No differences were noted between men and women patients and controls regarding the activity of the NF-kappaB gene, which encodes a protein that participates in a pro-inflammatory signaling pathway in white blood cells.
Likewise, the levels of two oxidative stress markers, thiobarbituric acid‑reactive species (fat oxidation) and urinary nitrite, were similar across all groups. A third marker for protein oxidation was lower in men with Fabry than controls.
“Our results suggest that long-term ERT in men with [Fabry] contributes to the reduction of a pro-inflammatory scenario and a decrease of oxidative damage in patients, reflecting greater control throughout the disease and in the multisystemic changes characteristic of this disorder,” the authors wrote.
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