Enzyme replacement therapy for Anderson-Fabry disease.

Area of Science:

• Genetics and Metabolism
• Rare Diseases
• Pharmacology

Background:

• Anderson-Fabry disease is an X-linked genetic disorder affecting glycosphingolipid metabolism.
• It leads to progressive renal insufficiency, cardiovascular complications, and reduced survival.
• Symptomatic female carriers also experience significant health issues.

Purpose of the Study:

• To evaluate the efficacy and safety of enzyme replacement therapy (ERT) for Anderson-Fabry disease.
• To compare ERT with placebo, no intervention, or other treatments.
• To synthesize evidence from randomized controlled trials (RCTs).

Main Methods:

• Searched major databases (Cochrane Library, MEDLINE, EMBASE, LILACS) and a specialized trials register up to September 2012.
• Included RCTs of agalsidase alfa or beta in diagnosed Anderson-Fabry disease patients.
• Two authors independently selected trials, assessed quality, and extracted data.

Main Results:

• Six trials with 223 participants were included.
• Agalsidase alfa showed no significant effect on biomarkers but improved pain scores and quality of life in some analyses.
• Agalsidase beta demonstrated significant improvements in biomarkers (kidney, heart, composite) but not mortality or pain; head-to-head comparison showed no significant difference in adverse events.

Conclusions:

• The current evidence from six small, low-quality RCTs is insufficient to robustly support the use of agalsidase alfa or beta for Anderson-Fabry disease.
• Further high-quality research is needed to establish the true efficacy and safety of ERT.
• The findings highlight the need for improved trial design in rare genetic disorders.