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Updated: Apr 17, 2026
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Published on: April 21, 2010
Blocking hyperactive androgen receptor signaling ameliorates cardiac and renal hypertrophy in Fabry mice
Jin-Song Shen1, Xing-Li Meng2, Mary Wight-Carter3
1Institute of Metabolic Disease, Baylor Research Institute, 3812 Elm Street, Dallas, TX 75226, USA jinsong.shen@baylorhealth.edu.
Abstract:
Fabry disease is caused by deficient activity of lysosomal enzyme α-galactosidase A. The enzyme deficiency results in intracellular accumulation of glycosphingolipids, leading to a variety of clinical manifestations including hypertrophic cardiomyopathy and renal insufficiency. The mechanism through which glycosphingolipid accumulation causes these manifestations remains unclear. Current treatment, especially when initiated at later stage of the disease, does not produce completely satisfactory results. Elucidation of the pathogenesis of Fabry disease is therefore crucial to developing new treatments. We found increased activity of androgen receptor (AR) signaling in Fabry disease. We subsequently also found that blockade of AR signaling either through castration or AR-antagonist prevented and reversed cardiac and kidney hypertrophic phenotype in a mouse model of Fabry disease. Our findings implicate abnormal AR pathway in the pathogenesis of Fabry disease and suggest blocking AR signaling as a novel therapeutic approach.
Insights
Fabry disease involves glycosphingolipid buildup due to alpha-galactosidase A deficiency. Blocking androgen receptor signaling reversed heart and kidney enlargement in a mouse model, suggesting a new therapeutic strategy.
Area of Science:
- Biochemistry
- Genetics
- Pathology
Background:
- Fabry disease stems from deficient alpha-galactosidase A activity, causing glycosphingolipid accumulation.
- This accumulation leads to organ damage, including hypertrophic cardiomyopathy and renal insufficiency.
- Current treatments are insufficient, especially in later disease stages, highlighting the need for new therapeutic targets.
Purpose of the Study:
- To investigate the underlying mechanisms of Fabry disease pathogenesis.
- To explore the role of androgen receptor (AR) signaling in Fabry disease.
- To evaluate AR signaling blockade as a potential therapeutic strategy for Fabry disease.
Main Methods:
- Assessed androgen receptor (AR) signaling activity in Fabry disease.
- Utilized a mouse model of Fabry disease.
- Investigated the effects of AR signaling blockade (castration and AR antagonists) on cardiac and renal hypertrophy.
Main Results:
- Fabry disease exhibits increased androgen receptor (AR) signaling activity.
- Blocking AR signaling prevented and reversed cardiac and kidney hypertrophy in the Fabry disease mouse model.
- These findings establish a link between AR pathway and Fabry disease pathology.
Conclusions:
- Abnormal androgen receptor (AR) pathway activation is implicated in Fabry disease pathogenesis.
- Blocking AR signaling represents a promising novel therapeutic approach for Fabry disease.
- Targeting the AR pathway could mitigate key Fabry disease manifestations like organ hypertrophy.
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