Misfolded Proteins in the Skin of People With Parkinson's Disease and Other Parkinsonism

Study Overview
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Brief Summary
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The purpose of this study is to determine whether identification of misfolded proteins in the skin will help to determine what sort of parkinsonism someone has. We seek to demonstrate whether someone has a synucleinopathy such as Parkinson's disease (PD), multiple system atrophy (MSA), or dementia with Lewy bodies(DLB), as opposed to a tauopathy such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD) or no parkinsonism at all (control).

Detailed Description
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This is a clinical research study for patients with parkinsonism, including Parkinson's disease, progressive supranuclear palsy, corticobasal degeneration, multiple system atrophy, and dementia with Lewy bodies. Parkinsonism can be difficult to diagnose, especially in the early stages of the disease. Skin punch biopsy could be a useful and way to diagnose and measure the severity of these conditions. Given that there currently is no proven way to determine that someone has a synucleinopathy such as PD and not a tauopathy, this is a novel study that may lead to better ways to diagnose people with parkinsonism. The purpose of the study is to identify changes on a skin punch biopsy, in which small samples of skin are removed and sent to the laboratory for examination. We are seeking to measure the amount of misfolded alpha-synuclein in someone's skin. Participation will last between 1 and 2 years and will involve between 2 and 4 visits. Visits will include a physical examination, questionnaires, a memory test, blood draws and saliva collection, and a single visit for skin punch biopsies. We will also be looking to enroll volunteers to serve as controls, who do not have any neurological illness.

Official Title
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Assessing Skin Biomarkers for Preclinical Diagnosis of PD and Non-PD Parkinsonism

Conditions
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Parkinson Disease, Parkinsonism, Dementia With Lewy Bodies, Multiple System Atrophy, Progressive Supranuclear Palsy, Corticobasal Degeneration

Intervention / Treatment
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* Procedure: punch skin biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 years old and age <90 years of age at the time of the baseline visit 1 Age of diagnosis at least 40 years old for PD, DLB, and PSP and at least 30 years old for MSA A confirmed diagnosis of PD, PSP, CBD, MSA, DLB, or healthy control Montreal Cognitive Assessment (MoCA) > 10 at the outset of the study Exclusion Criteria: Age 90 or above Allergy to local anesthetic History of deep brain stimulation (DBS) or other brain surgery prior to Visit 1 For PD or DLB diagnoses, any other neurodegenerative or central nervous system process that would interfere with examination For PD or DLB, history of negative DATscan Use of investigational drugs or devices within 60 days prior to baseline visit (except for dietary supplements) In control subjects, family history of a neurodegenerative disease in a first degree or second degree blood relative History of schizophrenia History of antipsychotic medication use or exposure in controls or history of antipsychotic medication leading to parkinsonism (drug induced parkinsonism) in the parkinsonism group Blood clotting disorder On multiple (more than one) antiplatelet and/or anticoagulant blood thinner medications in combination (except for aspirin if it can be safely held for 1 week) Any other medical, psychiatric, or cognitive illness that in the investigator's opinion would interfere with cooperation or ability to undergo the study procedures.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Parkinsonism Group<br>Participants with Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) | Procedure: punch skin biopsy<br>* An anesthetic medication is injected to numb the areas of skin and two samples of skin are obtained from punch biopsy.<br>|
| Control Group<br>Participants without parkinsonism | Procedure: punch skin biopsy<br>* An anesthetic medication is injected to numb the areas of skin and two samples of skin are obtained from punch biopsy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of alpha-synuclein in the skin | Alpha-synuclein will be measured by RT-QuIC and sPMCA | Cross-sectional at baseline | 
| Change in PSPRS measures of progressive supranuclear palsy (PSP) severity in people with PSP | Questionnaire and examination. Lower scores are better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in UMSARS measures of multiple system atrophy (MSA) severity in people with MSA | Questionnaire and examination. Lower scores are better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in Hoehn and Yahr (H&Y) and modified H&Y Scores | Zero to 5 parkinsonism rating scale score. Lower score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in Schwab and England (S&E) Score | 0% to 100% rating scale score. Higher score is better. | Baseline, 1 year, and optional 2 year assessment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Montreal Cognitive Assessment (MoCA) | Zero to 30 cognitive rating scale score. Higher score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in Epworth Sleepiness Scale (ESS) | Zero to 24 sleepiness rating scale score. Lower score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in Hamilton depression scale | 17 item depression rating scale score. Lower score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in Hamilton anxiety scale | 14 item depression rating scale score. Lower score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in REM Behavior Disorder Questionnaire | 10 item depression rating scale score. Lower score is better. | Baseline, 1 year, and optional 2 year assessment | 
| Change in blood pressure with orthostatic posture | Blood pressure from lying down to sitting to standing. Smaller drop in blood pressure is better. | Baseline, 1 year, and optional 2 year assessment | 
| Amount of alpha-synuclein in the blood | Alpha-synuclein will be measured in the blood sample | Baseline, optional 1 year assessment, and optional 2 year assessment | 
| Change in PDQ-39 | 39 item health status questionnaire. Lower is better. | Baseline, optional 1 year assessment, and optional 2 year assessment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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biomarker, Parkinson disease, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, parkinsonism, alpha-synuclein