Related Experiment Video
Updated: Apr 27, 2026
10:16
In Vitro Enzyme Measurement to Test Pharmacological Chaperone Responsiveness in Fabry and Pompe Disease
Published on: December 20, 2017
7.6K
Modeling changes in biomarkers in Gaucher disease patients receiving enzyme replacement therapy using a
Marie Vigan1, Jérôme Stirnemann, Catherine Caillaud
1INSERM, IAME, UMR 1137, INSERM, F-75018 Paris, France. marie.vigan@inserm.fr.
Orphanet Journal of Rare Diseases
|July 2, 2014
Summary
A new model tracks Gaucher disease (GD) biomarkers during enzyme replacement therapy (ERT). It shows biomarkers normalize within two years, but with significant patient variability, and identifies factors influencing treatment response.
Area of Science:
- Biochemistry
- Genetics
- Pharmacology
Background:
- Gaucher disease (GD) is a rare genetic disorder caused by deficient glucocerebrosidase enzyme activity.
- Biomarker elevations (ferritin, chitotriosidase) and decreases (hemoglobin, platelets) characterize GD.
- Enzyme replacement therapy (ERT) is a primary treatment, but dynamic biomarker response models are lacking.
Purpose of the Study:
- To develop a pathophysiological model for analyzing biomarker changes during ERT in Gaucher disease.
- To assess the impact of covariates on biomarker response to ERT.
- To provide insights into the kinetics of biomarker normalization under ERT.
Main Methods:
- Analysis of ferritin, chitotriosidase, hemoglobin, and platelet levels in French GD Registry patients on ERT.
- Application of a simplified exponential pathophysiological model to track biomarker changes.
- Evaluation of covariates including age, splenectomy, sex, genotype, and ERT dose.
Main Results:
- An exponential model demonstrated a good fit for biomarker data, with a biomarker normalization half-life of 0.5 years.
- Predicted steady-state biomarkers were 40% (ferritin), 10% (chitotriosidase), 120% (hemoglobin), and 200% (platelets) of initial levels.
- Age, sex, and splenectomy significantly affected initial biomarker concentrations and/or their variation amplitude.
Conclusions:
- The first dynamic model of biomarker changes during ERT for Gaucher disease was developed.
- 95% biomarker response to ERT is estimated within 2 years, despite high inter-patient variability.
- Current ERT is predicted to normalize chitotriosidase and ferritin in approximately 65% of patients.
