Establishing Treatment Effectiveness in Fabry Disease: Observation-Based Recommendations for Improvement.

Int J Mol Sci

Department of Endocrinology and Metabolism, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam UMC Location University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.

Published: September 2024

AI Article Synopsis

  • Fabry disease (FD) results from mutations in a specific gene that lead to a deficiency in the enzyme α-galactosidase A, causing harmful substrate accumulation, with symptoms varying widely between male and female patients.
  • Although FD therapies like enzyme replacement therapy (ERT) and chaperone therapy have been available for around 20 years, there is still limited evidence supporting their long-term effectiveness due to diverse patient populations and inconsistencies in study designs.
  • To improve future research on FD treatments, the review suggests better patient matching, international collaboration, and standardized approaches for evaluating treatment effectiveness, including clear recommendations for study outcomes and duration.

Article Abstract

Fabry disease (FD, OMIM #301500) is caused by pathogenic gene (OMIM #300644) variants, resulting in a deficiency of the α-galactosidase A enzyme with accumulation of its substrate globotriaosylceramide and its derivatives. The phenotype of FD is highly variable, with distinctive disease features and course in classical male patients but more diverse and often nonspecific features in non-classical and female patients. FD-specific therapies have been available for approximately two decades, yet establishing robust evidence for long-term effectiveness remains challenging. This review aims to identify the factors contributing to this lack of robust evidence for the treatment of FD with enzyme replacement therapy (ERT) (agalsidase-alfa and -beta and pegunigalsidase alfa) and chaperone therapy (migalastat). Major factors that have been identified are study population heterogeneity (concerning sex, age, phenotype, disease stage) and differences in study design (control groups, outcomes assessed), as well as the short duration of studies. To address these challenges, we advocate for patient matching to improve control group compatibility in future FD therapy studies. We recommend international collaboration and harmonization, facilitated by an independent FD registry. We propose a stepwise approach for evaluating the effectiveness of novel treatments, including recommendations for surrogate outcomes and required study duration.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11396259PMC
http://dx.doi.org/10.3390/ijms25179752DOI Listing

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