Gaucher Disease
Conditions
Brief summary
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.
Interventions
OTHERno intervention
no intervention, this is an observational study
Sponsors
University of Minnesota
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| EVs quantity | baseline | Examine EV quantities isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. |
| EVs size | baseline | Examine EV sizes isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. |
| EVs content | baseline | Examine contents in vesicles isolated from plasma samples collected from patients with GD and carriers and compare to healthy individuals. |
Countries
United States
Contacts
CONTACTReena Kartha, PhD, MS
CONTACTMarcia Terluk, PhD
PRINCIPAL_INVESTIGATORReena Kartha, PhD, MS
University of Minnesota
PRINCIPAL_INVESTIGATORSubbaya Subramanian, PhD, MS
University of Minnesota
Outcome results
None listed