The GBA Multimodal Study in Parkinson's Disease
Study Details
Study Description
Brief Summary
This study plans to analyze the molecular and clinical mechanisms of the relationship between the GBA mutations and Parkinson's disease. This will be assessed through the use of advanced neuroimaging techniques called PET (positron emission tomography) to study the accumulation of the tau protein and the dysfunction of acetylcholine and dopamine in the brain of people with a mutation in the GBA gene, with and without Parkinson's disease. The ingestigators will also use a technology-based assessment to study the typing patterns as possible biomarkers of early motor dysfunctions.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
Study Rationale: People who have a mutation in the GBA gene have a higher risk of developing Parkinson's disease (PD) and, if they have PD, are more likely to have cognitive decline and dementia. Cognitive problems in people with PD is related to dysfunction of the brain chemical acetylcholine and likely to the accumulation of the tau protein in the brain. Another observation in previous studies is that analyzing the patterns of typing into a computer can help differentiate healthy people from people with PD.
Hypothesis: The investigators hypothesize that people with GBA-related PD will have higher acetylcholine dysfunction and tau accumulation compared with non-GBA patients, and that these changes may start in the asymptomatic phase (i.e., people with the mutation but without symptoms of PD). The investigators also believe that the investigators will be able to detect subjects with higher degree of dopamine loss just by analyzing the way they type into a computer.
Study Design: The investigators will recruit 25 subjects with a GBA mutation (10 subjects with PD and 15 asymptomatic carriers). All the participants will have a clinical evaluation and a typing session, and subsequently will undergo a brain MRI and three PET scans with a tau tracer, an acetylcholine tracer, and a dopaminergic tracer. A blood sample will also be taken for the analysis of GCase (the enzyme related to the GBA mutation).
Impact on Diagnosis/Treatment of Parkinson's Disease: The results will help understand the changes that take place in the brain of people with GBA-related Parkinson's disease, and hopefully will shed light also on the pathophysiology of non-GBA-related Parkinson's, as well as on the molecular correlates of cognitive decline, especially in its early stage. The typing data along with dopaminergic imaging will clarify the possible role of using typing patterns to identify subjects with early stage Parkinson's disease.
Next Steps for Development: The findings of this study may help identify biomarkers for cognitive decline in early Parkinson's disease, with a potential role in clinical trials. Also, if the hypothesis on the typing is confirmed, this approach may be studied in larger cohorts for early diagnosis of Parkinson's in other at-risk populations.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| GBA-PD People with Parkinson's disease who are known heterozygous carriers of pathogenic GBA gene mutations. |
Diagnostic Test: PET scan
3 PET scans to analyze the dopamine metabolism, acetylcholine and tau protein deposition in the brain.
Diagnostic Test: neuroQWERTY
Analysis of free-text typing in a computer and/or a touch-screen device.
|
| Asymptomatic GBA Known heterozygous carriers/obligated carriers of pathogenic GBA gene mutations. |
Diagnostic Test: PET scan
3 PET scans to analyze the dopamine metabolism, acetylcholine and tau protein deposition in the brain.
Diagnostic Test: neuroQWERTY
Analysis of free-text typing in a computer and/or a touch-screen device.
|
Outcome Measures
Primary Outcome Measures
- Acetylcholinesterase activity [baseline]
11C-PMP PET
- Tau protein deposition [baseline]
11C-PBB3 PET
- Dopaminergic denervation [baseline]
11C-DTBZ PET
- neuroQWERTY index [baseline]
Typing analysis
Eligibility Criteria
Criteria
Inclusion Criteria:
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heterozygous for a pathogenic GBA mutation (e.g., p.L444P, p.N370S) or polymorphism;
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age 18 to 80 years.
Exclusion Criteria:
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co-occurrence of other neurological disorders;
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implants that contraindicate the MRI scanning (e.g. cardiac pacemaker, ferromagnetic implants or devices);
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severe claustrophobia;
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intolerance to antiparkinsonian drug withdrawal (for GBA-PD subjects);
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ongoing treatment with cholinergic drugs
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 2 | University of Washington | Seattle | Washington | United States | 98108-1595 |
| 3 | Pacific Parkinson's Research Centre | University of British Columbia | Vancouver | British Columbia | Canada |
Sponsors and Collaborators
- Pacific Parkinson's Research Centre
- University of British Columbia
- University of Washington
- Oregon Health and Science University
- Simon Fraser University
- Michael J. Fox Foundation for Parkinson's Research
- Silverstein Foundation
- Weston Brain Institute
Investigators
- Principal Investigator: Michele Matarazzo, MD, Pacific Parkinson's Research Centre | University of British Columbia
- Principal Investigator: A. Jon Stoessl, CM, MD, FRCPC, FCAHS, Pacific Parkinson's Research Centre | University of British Columbia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 16451