Molecular and Cellular Mechanisms of Lysosomal Storage Diseases

Investigation of Molecular and Cellular Mechanisms of Lysosomal Storage Diseases

The lysosome is a specialized part of the cell that functions to degrade metabolic wastes in the cell. Defects in the functioning of the lysosome result in accumulation and subsequent storage of such metabolic wastes. These defects lead to conditions known as lysosomal storage diseases (LSD). LSDs are caused by inherited genetic mutations and there are over 40 genetically distinct lysosomal storage diseases. Within each specific lysosomal storage disease there are variances in severity of disease, age of onset, and clinical presentation. Though the genetic mutations contributing to the disease have been largely clarified, the molecular and cellular mechanisms that contribute to variations in each distinct LSD remain unclear. With this study we intend to better understand at the cellular and molecular level how the accumulation and storage of metabolic wastes in the lysosome affect the clinical manifestation of LSDs, to detect changes in these mechanisms upon treatment administration, and to correlate these results to genetic information. The knowledge obtained from this research study could lead to better ways to diagnose and treat lysosomal storage diseases.

Study Overview

• Status: Unknown
• Conditions: Lysosomal Storage Disorders

• Study Type: Observational
• Enrollment (Anticipated): 80

Contacts and Locations

• Study Contact: Name: Ozlem Goker-Alpan, MD; Phone Number: 571-308-1904; Email: ogoker-alpan@ldrtc.org
• Study Contact Backup: Name: Renuka Limgala, PhD; Phone Number: 703-261-6220; Email: rlimgala@ldrtc.org

Study Locations

• United States
  • Virginia
    • Fairfax, Virginia, United States, 22030
      • Recruiting
      • Lysosomal and Rare Disorders Research and Treatment Center, Inc (LDRTC)
      • Contact: Renuka Limgala, PhD; Phone Number: 703-261-6220; Email: rlimgala@ldrtc.org
      • Contact: Ozlem Goker-Alpan, M.D.; Phone Number: 571-308-1900; Email: ogoker-alpan@ldrtc.org
      • Sub-Investigator: Renuka P Limgala, PhD
      • Sub-Investigator: Margarita M Ivanova, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 100 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients or suspected carriers of a lysosomal storage disorders.

Description

Inclusion Criteria:

• Subject is greater than or equal to 1 day of age and less than or equal to 100 years of age
• Signed Informed Consent/Assent
• Subject is able and willing to comply with study protocol requirements.
• From clinical or blood laboratory findings subject has evidence of a lysosomal storage disease or a family member of a patient with lysosomal storage disease

Exclusion Criteria:

• Pregnant woman

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlating genetic mutations with clinical signs and symptoms	Genetic information (DNA) will be collected from biological samples (e.g. blood, skin cells) and correlated with clinical signs and symptoms. DNA will be sequenced in order to identify a specific mutation. Fluorescence assay will be performed to measure the enzyme activity of the affected protein. Physical examination will be performed, and supporting test results will be collected for identifying the signs and symptoms of the particular disorder.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Associated Immune Pathophysiology	Blood will be collected for identifying alterations in the innate and adaptive immune system. Flow cytometry will be used to analyze cell surface and intracellular biomarkers on immune cells such as B-cells, T-cells, eosinophils.	5 years

Collaborators and Investigators

• Sponsor: O & O Alpan LLC
• Investigators: Principal Investigator: Ozlem Goker-Alpan, MD, Lysosomal & Rare Disorders Research & Treatment Center (LDRTC)

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2013
• Primary Completion (ANTICIPATED): December 1, 2021
• Study Completion (ANTICIPATED): December 1, 2022

Study Registration Dates

• First Submitted: November 25, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (ESTIMATE): December 4, 2013

Study Record Updates

• Last Update Posted (ACTUAL): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 22, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Gaucher disease; Fabry disease; Pompe disease; Niemann-Pick disease
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases
• Other Study ID Numbers: 13-CFCT-07