Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease

Study Overview
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Brief Summary
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International, multicenter, epidemiological study to demonstrate the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients and to correlate lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3

Detailed Description
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Gaucher disease is an autosomal recessive inherited lysosomal storage disorder. The disease is caused by the hereditary deficiency of the glucocerebrosidase, a lysosomal enzyme that breaks down glucocerebroside into glucose and ceramide. To date a definitive diagnosis of Gaucher's disease can only be made applying biochemical testing measuring the reduced enzymatic activity of the beta-glucosidase together with genetic confirmation. Since numerous different mutations may be the cause of a particular lysosomal storage disease the sequencing of the entire beta-glucosidase gene is applied in Gaucher's disease in order to confirm the genetic diagnosis. The use of primary storage molecules as biomarker was assessed for glucosylceramide (Gb1) in plasma of Gaucher's disease patients and compared to the level of Gb1 in healthy individuals. In order to establish a sensitive and specific biomarker for GD, we compared mass spectra of the plasma of healthy controls and GD patients using HPLC and tandem mass spectrometry. Mass spectra that differed most between patients and controls were analysed in more detail. The resulting biomarker, which was patented in June 2011 (PCT/EP2012/002409), was lyso - Gb1. We identified this compound as a reliable, sensitive and specific biomarker for GD in a cohort of GD patients. Furthermore, in a pilot study we evaluated whether lyso-Gb1 is related to the specific genotypes and is reliable for long-term monitoring of the efficiency of therapy. The aim this study is therefore to investigate lyso-Gb1 as a long-term prognostic marker in naïve, non-ERT/SRT GD type 1 patients by monitoring over the course of 36 months.

Official Title
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Lyso-Gb1 as a Long-term Prognostic Biomarker in Gaucher Disease: An International, Multicenter, Epidemiological Protocol

Conditions
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Lysosomal Storage Diseases, Gaucher Disease, Sphingolipidoses

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 6 months or older Patients with genetically confirmed diagnosis of Gaucher disease type 1 No prior treatment with enzyme replacement therapy or substrate reduction therapy ro no traetment for more than 24 months Signed informed consent by parents/legal guardian and patient Exclusion Criteria: Male or female patients being younger than 6 months Patients without genetically confirmed diagnosis of Gaucher disease type 1 Gaucher disease 2 or 3 Patient is currently undergoing enzyme replacement therapy or substrate reduction therapy Missing signed informed consent

Ages Eligible for Study
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Minimum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants diagnosed with Gaucher disease<br>Participants with genetically confirmed diagnosis of Gaucher disease type 1 older than 6 months old | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrating the correlation and predictive value of lyso-Gb1 concentration with the clinical severity of naïve, initially non-ERT/SRT Gaucher disease type 1 and during the study ERT/SRT-newly started Gaucher type 1 patients | lyso-Gb1 will be analzyed via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC. | 48 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlating lyso-Gb1 concentration with the clinical improvement of ERT or SRT treated Gaucher type 1 and the clinical course of non-treated patients based on GD-DS3. | lyso-Gb1 will be analysed over a period of 36 months via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) to demonstrate the course of the biomarker. | 48 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gaucher Disease type 1, Lymphatic Diseases, Lipid Metabolism, Inborn Errors, Lipid Metabolism Disorders, Lipidoses