Clinical trial NCT05843552: Extracellular Vesicles as Potential Biomarkers and Therapeutic Target in Gaucher Disease
Official title: Extracellular Vesicles as Potential Biomarkers and Therapeutic Target in Gaucher Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gaucher Disease
Lead sponsor: University of Minnesota
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with GD (n=10 untreated), obligate carriers (n=10) and healthy volunteers (frequency matched for age and gender; n=10) for this study. In the next phase of this project, we will examine the effect of GD treatment on EV characteristics by focusing on patients who are currently being treated and compare various therapies and correlate it with established biomarkers.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: EVs quantity
timeFrame: baseline
measure: EVs quantity
timeFrame: 3months
measure: EVs size
timeFrame: baseline
measure: EVs size
timeFrame: 3months
measure: EVs content
timeFrame: baseline
measure: EVs content
timeFrame: 3months
Secondary outcomes:
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Reena Kartha, PhD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Subbaya Subramanian, PhD, MS
role: PRINCIPAL_INVESTIGATOR
References: