Biomarker Analysis for GBA Associated Parkinson's Disease

NCT03811496 | Unknown

• 1 other identifier: 18-LDRTC-01
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The primary aim of the study is to conclusively demonstrate the possibility of using the following molecules, α-Synuclein, LRRK2 and Parkin individually or in combination as biomarkers for Parkinson's disease (PD) progression in patients/ carriers of Gaucher disease (GD). All the assays will be performed only using peripheral blood, thus the identification of a peripheral marker that can be used in both diagnosis and prognosis of the disease and symptom severity would lead to a fast, efficient and reliable assay that can be performed on an easily accessible tissue type outside of the brain. It is now known that patients with GD, even carriers with one mutated GBA gene (OMIM 606463) are at a higher risk for developing PD, and at an earlier age. In an attempt to assess whether GBA alterations would also impact α-Synuclein and Parkin metabolism in humans, the expression at both molecular and protein level in the peripheral blood mononuclear cells (PBMCs) will be investigated.

Conditions

Parkinson Disease; Gaucher Disease

Keywords

Parkinson disease; Gaucher disease; GBA gene; alpha-synuclein

Outcome Measures

Primary Outcomes (6)

• Gene expression levels of SNCA

  Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of SNCA.

  18 months

• Gene expression levels of LRRK2

  Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of LRRK2.

  18 months

• Gene expression levels of Parkin

  Gene expression levels relative to internal reference genes will be compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression of Parkin.

  18 months

• Protein expression levels of alpha-synuclein

  Protein expression levels of alpha-synuclein will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.

  18 months

• Protein expression levels of LRRK2

  Protein expression levels of LRRK2 will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.

  18 months

• Protein expression levels of Parkin

  Protein expression levels of Parkin will be analyzed using flow cytometry and compared between the individual subjects as well as grouped analysis to identify a specific pattern in alterations in level of expression.

  18 months

Study Arms (3)

GD-PD

Patients and carriers of Gaucher disease with confirmed mutations in GBA gene who have developed Parkinson's disease symptoms

GD-nonPD

Patients with Gaucher disease but no known Parkinson's symptoms

nonGD-nonPD

Non-Gaucher disease/healthy controls

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Study will include three cohorts: 1. Patients and carriers of Gaucher disease with confirmed mutations in GBA gene who have developed Parkinson's disease symptoms (GD-PD), 2. Patients with Gaucher disease but no known Parkinson's symptoms (GD-nonPD) and 3. Non-Gaucher disease/healthy controls (nonGD-nonPD). All participants will be recruited after obtaining informed consent using IRB (Independent Review Board) approved informed consent form.

You may qualify if:

• The study will include
• adult subjects age 21 or older with Gaucher disease with and without parkinsonism and individuals from families with a Gaucher proband and a history of parkinsonism.
• Controls will include unaffected siblings of patients with Gaucher disease and subjects with sporadic PD, without glucocerebrosidase mutations, and healthy volunteers who do not have a family history of parkinsonism or Gaucher disease.

You may not qualify if:

• Subjects excluded from the study include those who:
• present with severe cognitive deficits impairing decision making
• are unable to or for whom it is medically unsafe to withdraw from their current medications, such as subjects on SSRI s and other psychoactive drugs. The subjects on SSRIs may be included in the study only with an approval from the prescribing physician to discontinue their medications temporarily for the study.
• are pregnant or nursing. All women of child bearing potential will undergo a pregnancy test.
• have a history of neurologic conditions such as stroke or any focal brain lesion that may result in parkinonian manifestations. Individuals with such MRI findings will be excluded from the study.

Sponsors & Collaborators

• Lysosomal and Rare Disorders Research and Treatment Center, Inc.: lead

Study Sites (1)

LDRTC

Fairfax, Virginia, 22030, United States

RECRUITING

Related Links

• Institute website for more details

MeSH Terms

Conditions

Parkinson Disease; Gaucher Disease; Parkinson Disease 4, Autosomal Dominant Lewy Body

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Ozlem Goker-Alpan, MD

  LDRTC

  PRINCIPAL INVESTIGATOR

• Renuka Limgala, PhD

  LDRTC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Renuka Limgala, PhD

CONTACT

2407155382; rlimgala@ldrtc.org

Ozlem Goker-Alpan, MD

CONTACT

7032616220; ogoker-alpan@ldrtc.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 18, 2019
• First Posted: January 22, 2019
• Study Start: February 1, 2018
• Primary Completion: February 1, 2020
• Study Completion: July 1, 2020
• Last Updated: January 23, 2019

Record last verified: 2019-01

Locations

US (1)