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

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

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).

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Parkinsonism; Multiple System Atrophy; Corticobasal Degeneration; Progressive Supranuclear Palsy; Dementia With Lewy Bodies
• Intervention / Treatment: Procedure: punch skin biopsy

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 184

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • South Euclid, Ohio, United States, 44121
      • University Hospitals Suburban Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

People with parkinsonism, Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), and also controls without parkinsonism.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Parkinsonism Group; 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; An anesthetic medication is injected to numb the areas of skin and two samples of skin are obtained from punch biopsy.
Control Group; Participants without parkinsonism	Procedure: punch skin biopsy; An anesthetic medication is injected to numb the areas of skin and two samples of skin are obtained from punch biopsy.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospitals Cleveland Medical Center
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); University of Bologna; National Institute of Neurological Disorders and Stroke (NINDS); Case Western Reserve University; Universidad Autonoma de San Luis Potosí; Banner Health
• Investigators: Principal Investigator: Steven Gunzler, MD, University Hospitals Cleveland Medical Center and Case Western Reserve University; Principal Investigator: Chen Shu, PhD, University of Alabama at Birmingham; Principal Investigator: Zerui Wang, MD, PhD, Case Western Reserve University; Principal Investigator: Qingzhong Kong, PhD, Case Western Reserve University

Study record dates

Study Major Dates

• Study Start (Actual): March 12, 2019
• Primary Completion (Actual): May 31, 2025
• Study Completion (Actual): May 31, 2025

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: biomarker; parkinsonism; Parkinson's disease; Parkinson disease; dementia with Lewy bodies; multiple system atrophy; progressive supranuclear palsy; corticobasal degeneration; alpha-synuclein
• Additional Relevant MeSH Terms: Synucleinopathies; Neurologic Manifestations; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Pathological Conditions, Anatomical; Neurocognitive Disorders; Eye Diseases; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Cranial Nerve Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Ophthalmoplegia; Ocular Motility Disorders; Paralysis; Hypotension; Corticobasal Degeneration; Parkinson Disease; Atrophy; Multiple System Atrophy; Shy-Drager Syndrome; Dementia; Supranuclear Palsy, Progressive; Lewy Body Disease; Parkinsonian Disorders
• Other Study ID Numbers: 20181189; 1U01NS112010-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No