Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey
Abstract Background Patients with Gaucher disease (GD) require continual monitoring; however, lack of specific disease biomarkers was a significant challenge in the past. Glucosylsphingosine (lyso-Gb1) has been shown to be a reliable, key, specific, and sensitive biomarker for diagnosis, prognosis,...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-01-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-024-03444-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571290758676480 |
|---|---|
| author | Ari Zimran Shoshana Revel-Vilk Tama Dinur Majdolen Istaiti Jaco Botha Elena Lukina Pilar Giraldo Patrick Deegan Stephan vom Dahl |
| author_facet | Ari Zimran Shoshana Revel-Vilk Tama Dinur Majdolen Istaiti Jaco Botha Elena Lukina Pilar Giraldo Patrick Deegan Stephan vom Dahl |
| author_sort | Ari Zimran |
| collection | DOAJ |
| description | Abstract Background Patients with Gaucher disease (GD) require continual monitoring; however, lack of specific disease biomarkers was a significant challenge in the past. Glucosylsphingosine (lyso-Gb1) has been shown to be a reliable, key, specific, and sensitive biomarker for diagnosis, prognosis, and treatment response in clinical studies of patients with GD. We evaluated the change in lyso-Gb1 concentration over time following enzyme replacement therapy in patients with confirmed GD using real-world data from the Gaucher Outcome Survey disease registry. Methods Data for patients aged ≥ 18 years with a confirmed diagnosis of GD and at least two lyso-Gb1 assessments were analyzed retrospectively. Patients were stratified by treatment status at baseline (time of first lyso-Gb1 assessment). Lyso-Gb1 concentrations were measured from dried blood spot (DBS) samples by Centogene AG. Assessments included change in lyso-Gb1 concentration, hemoglobin concentration, platelet counts, and spleen and liver volume from baseline to the last lyso-Gb1 assessment. Results Of 2007 patients enrolled in the Gaucher Outcome Survey as of February 25, 2022, 435 met the inclusion criteria and were included in the study: 318 treated (‘all treated’; 277 receiving treatment at baseline, 41 treatment naive at baseline), 38 receiving treatment at baseline who stopped treatment before the last lyso-Gb1 assessment, and 79 untreated. Lyso-Gb1 concentrations decreased from baseline to the last lyso-Gb1 assessment for all treated patients (median change − 8.6 ng/mL), and increased for untreated patients (median change 25.0 ng/mL) and those who stopped treatment (median change 19.5 ng/mL). Decreases were greater for all treatment-naive than previously treated patients (median change − 120.5 vs. − 3.3 ng/mL) and for velaglucerase alfa–treated patients vs. the overall treated cohort (–32.6 vs. − 8.6 ng/mL). Small improvements in hemoglobin concentrations, platelet counts, and spleen volume were observed for treated patients but not untreated/stopped treatment cohorts. Conclusions In this study, changes in lyso-Gb1 concentrations from DBS were reflective of responses to enzyme replacement therapy initiation or withdrawal in most patients. These findings confirm that the use of DBS samples for routine monitoring of lyso-Gb1 concentrations in patients with GD is feasible in real-world settings and may be useful to assess treatment response. |
| format | Article |
| id | doaj-art-2eaac2cf00d148d9bc5d8cc81b4eaba2 |
| institution | Kabale University |
| issn | 1750-1172 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj-art-2eaac2cf00d148d9bc5d8cc81b4eaba22025-02-02T12:42:23ZengBMCOrphanet Journal of Rare Diseases1750-11722025-01-0120111010.1186/s13023-024-03444-yEvaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome SurveyAri Zimran0Shoshana Revel-Vilk1Tama Dinur2Majdolen Istaiti3Jaco Botha4Elena Lukina5Pilar Giraldo6Patrick Deegan7Stephan vom Dahl8Gaucher Unit, The Eisenberg R & D Authority, Shaare Zedek Medical CenterGaucher Unit, The Eisenberg R & D Authority, Shaare Zedek Medical CenterGaucher Unit, The Eisenberg R & D Authority, Shaare Zedek Medical CenterGaucher Unit, The Eisenberg R & D Authority, Shaare Zedek Medical CenterTakeda Pharmaceuticals International AGDepartment of Orphan Diseases, National Research Center for HematologyTranslational Research Unit, IIS AragonDepartment of Medicine, Addenbrookes Hospital, University of CambridgeDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital, Heinrich- Heine UniversityAbstract Background Patients with Gaucher disease (GD) require continual monitoring; however, lack of specific disease biomarkers was a significant challenge in the past. Glucosylsphingosine (lyso-Gb1) has been shown to be a reliable, key, specific, and sensitive biomarker for diagnosis, prognosis, and treatment response in clinical studies of patients with GD. We evaluated the change in lyso-Gb1 concentration over time following enzyme replacement therapy in patients with confirmed GD using real-world data from the Gaucher Outcome Survey disease registry. Methods Data for patients aged ≥ 18 years with a confirmed diagnosis of GD and at least two lyso-Gb1 assessments were analyzed retrospectively. Patients were stratified by treatment status at baseline (time of first lyso-Gb1 assessment). Lyso-Gb1 concentrations were measured from dried blood spot (DBS) samples by Centogene AG. Assessments included change in lyso-Gb1 concentration, hemoglobin concentration, platelet counts, and spleen and liver volume from baseline to the last lyso-Gb1 assessment. Results Of 2007 patients enrolled in the Gaucher Outcome Survey as of February 25, 2022, 435 met the inclusion criteria and were included in the study: 318 treated (‘all treated’; 277 receiving treatment at baseline, 41 treatment naive at baseline), 38 receiving treatment at baseline who stopped treatment before the last lyso-Gb1 assessment, and 79 untreated. Lyso-Gb1 concentrations decreased from baseline to the last lyso-Gb1 assessment for all treated patients (median change − 8.6 ng/mL), and increased for untreated patients (median change 25.0 ng/mL) and those who stopped treatment (median change 19.5 ng/mL). Decreases were greater for all treatment-naive than previously treated patients (median change − 120.5 vs. − 3.3 ng/mL) and for velaglucerase alfa–treated patients vs. the overall treated cohort (–32.6 vs. − 8.6 ng/mL). Small improvements in hemoglobin concentrations, platelet counts, and spleen volume were observed for treated patients but not untreated/stopped treatment cohorts. Conclusions In this study, changes in lyso-Gb1 concentrations from DBS were reflective of responses to enzyme replacement therapy initiation or withdrawal in most patients. These findings confirm that the use of DBS samples for routine monitoring of lyso-Gb1 concentrations in patients with GD is feasible in real-world settings and may be useful to assess treatment response.https://doi.org/10.1186/s13023-024-03444-yLyso-Gb1GlucosylsphingosineGaucher diseaseBiomarker |
| spellingShingle | Ari Zimran Shoshana Revel-Vilk Tama Dinur Majdolen Istaiti Jaco Botha Elena Lukina Pilar Giraldo Patrick Deegan Stephan vom Dahl Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey Orphanet Journal of Rare Diseases Lyso-Gb1 Glucosylsphingosine Gaucher disease Biomarker |
| title | Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey |
| title_full | Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey |
| title_fullStr | Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey |
| title_full_unstemmed | Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey |
| title_short | Evaluation of Lyso-Gb1 as a biomarker for Gaucher disease treatment outcomes using data from the Gaucher Outcome Survey |
| title_sort | evaluation of lyso gb1 as a biomarker for gaucher disease treatment outcomes using data from the gaucher outcome survey |
| topic | Lyso-Gb1 Glucosylsphingosine Gaucher disease Biomarker |
| url | https://doi.org/10.1186/s13023-024-03444-y |
| work_keys_str_mv | AT arizimran evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT shoshanarevelvilk evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT tamadinur evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT majdolenistaiti evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT jacobotha evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT elenalukina evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT pilargiraldo evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT patrickdeegan evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey AT stephanvomdahl evaluationoflysogb1asabiomarkerforgaucherdiseasetreatmentoutcomesusingdatafromthegaucheroutcomesurvey |