Fabry disease, an X-linked rare disease, is characterized by deficient expression and activity of alpha-galactosidase A and consequent lysosomal accumulation of Gb3 and derivatives in various organs. First-line treatment includes enzyme replacement therapy (ERT). However, Fabry disease is progressive and is associated with serious cardiovascular, renal, and cerebral complications, particularly in patients with late diagnosis, suggesting the involvement of secondary parallel mechanisms to Gb3 accumulation.
Previous studies have shown that patients with Fabry disease have increased and active oxidative stress that plays a primary role in the induction of cardiovascular-renal remodeling and related to left ventricular hypertrophy (LVH) seen in patients with Fabry disease. Other studies have demonstrated significant reductions in oxidative stress-related cell signaling mechanisms with antioxidant treatment with green tea in patients with chronic kidney disease stage 3-4 and those on dialysis, thus improving LVH.
Giovanni Bertoldi and colleagues conducted a study to test the hypothesis that treating patients with Fabry disease with green tea in combination with ERT would have additive positive effects toward oxidative stress and oxidative stress-induced cardiovascular and renal remodeling using a molecular biologic approach. Results were reported at the ERA 59th Congress in a presentation titled Effect of Green Tea on Top of Enzyme Replacement Therapy in Patients With Fabry Disease: A Molecular Biology Approach.
The study enrolled ten patients with Fabry disease. The status of oxidative stress was evaluated ex vivo in mononuclear cells prior to ERT, after 12 months of ERT, and after 6 months of additional treatment with two capsules of green tea (600 mg Camellia Sinensis leaves dry extract, 40% Epigallocathechinegallate, Frama S. r. I., Noventa Padovana, Italy) per day taken in the morning at fast in combination with ERT.
Oxidative stress was evaluated and compared in the three time periods in terms of protein expression of p22phox (subunit of NADH/NADPH oxidase essential for the production of superoxide), phosphorylation state of MYPT-1 (regulatory subunit of the myosin light chain phosphatase), ERK 1/2 (effectors at nuclear level of cardiovascular modality), and plasma levels of MDA (marker of lipid peroxidation). HO-1 levels (antioxidant and protective from oxidative stress) were also evaluated.
After 12 months of ERT, there was significant decrease in p22phox; after 6 months of add-on green tea treatment, there was further decrease. There were also significant decreases in MYPT-1 phosphorylation. After 12 months of ERT, the phosphorylation of ERK 1/2 remained unchanged; after 6 months of supplementation with green tea, there was significant decrease in phosphorylation of ERK 1/2 as well as in MDA levels. There was significant increase in HO-1 with both ERT and green tea supplementation.
In summary, the authors said, “This study provides data pointing toward an antioxidant effect exerted by ERT itself, which is further amplified by the treatment with green tea on top of ERT. These data while on one hand highlight the fundamental importance of an early diagnosis and treatment of Fabry disease, on the other hand suggest the need of adjuvant antioxidant treatments to prevent or improve specific disease manifestations.”
Source: Bertoldi G, Carrano G, Ravarotto V, et al. Effect of green tea on top of enzyme replacement therapy in patients with Fabry disease: a molecular biology approach. Abstract of a presentation at the 59th European Renal Association Congress (M0024), Paris, France, May 19-22, 2022.