Extracellular Vesicles as Potential Biomarkers and Therapeutic Target in Gaucher Disease

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.

Study Overview

• Status: Recruiting
• Conditions: Gaucher Disease
• Intervention / Treatment: Other: no intervention

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Reena Kartha, PhD, MS; Phone Number: 612-626-2436; Email: rvkartha@umn.edu
• Study Contact Backup: Name: Marcia Terluk, PhD; Phone Number: 612-625-7972; Email: mrterluk@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Recruiting
      • University of Minnesota
      • Contact: Reena Kartha, PhD, MS; Phone Number: 612-626-2436; Email: rvkartha@umn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
healthy volunteers	Other: no intervention; no intervention, this is an observational study
patients with GD	Other: no intervention; no intervention, this is an observational study
obligate carriers	Other: no intervention; no intervention, this is an observational study

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Minnesota
• Investigators: Principal Investigator: Reena Kartha, PhD, MS, University of Minnesota; Principal Investigator: Subbaya Subramanian, PhD, MS, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 31, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Actual): May 6, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease
• Other Study ID Numbers: EV

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No