Extracellular Vesicles as Potential Biomarkers and Therapeutic Target in Gaucher Disease

Study Overview
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Brief Summary
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This is an observational study intended to generate preliminary data to understand how lysosomal dysfunction can affect the biogenesis of extracellular vesicles, its content and function. The primary objective of the proposed project is to decipher how extracellular vesicle (EV) biogenesis and its role in intercellular communication can be impaired as a consequence of defects in lysosomal function. Collectively these defects in EV biogenesis and function can contribute to the neuroinflammation observed in lysosomal storage diseases. Since EVs can cross the blood-brain barrier, their characterization may be valuable in identifying novel biomarkers. In the presence of a GBA1 mutation, the decrease in GCase activity will lower overall lysosome function and increase the secretion of EVs. Further, there will be differences in EV size, its cargo including lipids, RNA and proteins and their aggregates. In comparison to healthy controls, EVs isolated from patients with Gaucher disease (GD) and GBA1 carriers is hypothesized to show significant differences in terms of its characteristics and content, which can contribute to our understanding of the link between lysosomes and neurological disease.

Official Title
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Extracellular Vesicles as Potential Biomarkers and Therapeutic Target in Gaucher Disease

Conditions
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Gaucher Disease

Intervention / Treatment
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* Other: no intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18-80yrs Restricted to participants who are untreated, obligate carriers and healthy controls. Participants with GD should have confirmed GD diagnosis, mutation confirmed for carriers and healthy controls confirmed to have no GBA1 mutation by gene sequencing. Exclusion Criteria: Exclude participants who have any hematological malignancy or other uncontrolled comorbid conditions. Exclude participants who are currently on therapy for their GD Exclude participants who have any hematological malignancy or other uncontrolled comorbid conditions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with GD<br> | Other: no intervention<br>* no intervention, this is an observational study<br>|
| obligate carriers<br> | Other: no intervention<br>* no intervention, this is an observational study<br>|
| healthy volunteers<br> | Other: no intervention<br>* no intervention, this is an observational study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EVs quantity | Examine EV quantities isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | baseline | 
| EVs quantity | Examine EV quantities isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | 3months | 
| EVs size | Examine EV sizes isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | baseline | 
| EVs size | Examine EV sizes isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | 3months | 
| EVs content | Examine contents in vesicles isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | baseline | 
| EVs content | Examine contents in vesicles isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. | 3months |