Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.

May 1, 2021 updated by: Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí

Parkinson's disease (PD) is a degenerative disease that can be difficult to diagnose. The clinicopathological studies had demonstrated a 76% accuracy in the clinical diagnosis of PD.

At the beginning of PD is difficult for the clinician to distinguish from Parkinsonism Plus Syndromes (PPS) due to the similarity of symptoms and the lack of specific diagnostic tests.

Specific biomarkers to help improve the accuracy of diagnosis and to separate these two entities are highly needed

The histological hallmark for definite diagnosis of PD is the presence of fibrillar aggregates of phosphorylated alpha-synuclein called Lewy bodies (LBs) and Lewy neurites. Previous autopsy-based studies have revealed that alpha-synuclein is deposited in the peripheral autonomic nervous system including the enteric nervous system of the alimentary tract, cardiac plexus, adrenal medulla and skin.

For this reason, in patients with parkinsonism, an alternative tool could be to demonstrate alpha-synuclein fibrillar aggregates in the skin, allowing early and appropriate diagnosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Parkinsonism, the syndrome, is a common movement disorder, and Parkinson's disease, the most common cause of parkinsonism, is the second most prevalent neurodegenerative disease after Alzheimer's disease.

The clinical diagnosis of PD is based on the presence of the four common features: tremor when the limb is at rest, resistance to passive movement of the joints (rigidity), slowness and paucity of movement (bradykinesia and akinesia) and postural abnormalities.

Approximately 25 percent of patients who received an initial clinical diagnosis of PD are found to have parkinsonism as part of another disorder, such as one of the so-called Parkinsonism-Plus Syndromes (PPS) The number and complexity of PPS seem to be increasing. This, along with the lack of diagnostic tests, makes it difficult for the clinician to distinguish between disease types.

Some characteristic clinical features are used for the differential diagnosis, this manifestations include early and severe postural instability, falls in the first year of onset, abnormal eye movements, autonomic dysfunction, cerebellar signs and upper motor neuron signs. The PPS respond poorly to antiparkinsonian medications and have a worse prognosis than does PD. In spite of these suggestive features, not all PD patients have the same progression, in some cases it is impossible to separate typical PD from PPS, especially at the early stage. In this context, biological markers must be of great usefulness for the differential diagnosis of these entities.

Some reports have described early features of PD such as (SPECT) imaging of the dopamine transporter that demonstrated the reduction of dopamine transporter in the striatum body at the early stage of PD and degeneration of the cardiac sympathetic nerve at the beginning of the disease process of PD; this occurs before neuronal cell loss is present in the dorsal vagal nucleus; This fact accounts for reduced cardiac uptake of meta-iodobenzylguanidine (MIBG), a physiological analog of norepinephrine. However, these diagnostic methods are not often performed. Therefore, more sensitive methods are needed to help improve the accuracy of diagnosis of PD.

Study Type

Observational

Enrollment (Actual)

87

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • San Luis Potosi, Mexico, 78290
        • Hospital Central Dr. Ignacio Morones Prieto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 95 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The patients will be selected from the department of neurology and the office of the principal investigator.

Description

Inclusion Criteria:

  • Clinical diagnosis of Parkinson's Disease or Parkinson Plus Syndrome
  • Subject is a male or female between the age of 50 and 95
  • Subject will write the informed consent

Exclusion Criteria:

  • History of stroke or/and trauma
  • Signs of cerebrovascular pathology
  • Brain tumor
  • Severe unrelated neurological or physical disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
PD Parkinson´s Disrease
We are studying the presence of alpha-synuclein in the epidermis and dermis besides the end nerve terminal. We have several reports until now, and we are following the study because we wish to convince the academic and scientific society over the utility of this study to be close to the molecular diagnosis of this kind of disease.
Procedure: Biopsy of skin
Under local anesthesia with 1% xylocaine, 4-mm punch biopsies with 3-mm depth, including the dermis and subcutaneous fat tissue, will undergone from two regions, neck and lower back.
AP Atypical Parkinsonism
with neurodegenerative disease (proteinopathies) and secondary AP.
Control group
Subjects without neurodegenerative disease and apparently good health status with an age that matches the problems groups

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Demonstrate the Presence of Alpha-Synuclein Inclusions in the Skin of Parkinson's Disease and Compare With an Atypical Parkinsonism Group and With a Healthy Control Group.
Time Frame: An average of seven days.

The presence in the brain of a-synuclein containing Lewy neurites, or bodies, is the histological hallmark of Parkinson's disease (PD).

The discovery of alpha-synuclein aggregates in nerve endings of the heart, digestive tract, and skin has lent support to the concept of PD as a systemic disease.

First, our goal was to demonstrate the presence of alpha-synuclein inclusions in the skin of PD patients.

Second, to detect quantitative differences (measures in the percentage of presence in the skin´s cells) between patients with PD, atypical parkinsonism (AP), compared with an apparent healthy group.
An average of seven days.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Autonoma de San Luis Potosí

Investigators

  • Principal Investigator: Ildefonso Rodríguez-Leyva, MD, Hospital Central "Dr. Ignacio Morones Prieto"
  • Study Director: Maria E Jimenez-Capdeville, PhD, Universidad Autonoma de San Luis Potosí
  • Study Director: Juan P Castanedo-Cazares, MD, Hospital Dr. Ignacio Morones Prieto
  • Study Chair: Erika G Chi-Ahumada, MC, Facultad de Medicina, UASLP
  • Study Chair: Maria E Jimenez-Capdeville, PhD, Facultad de Medicina
  • Study Chair: Robert A. Norman, MD, PhD., Independent Dermatologist

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2011

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

October 1, 2014

Study Registration Dates

First Submitted

June 17, 2011

First Submitted That Met QC Criteria

June 23, 2011

First Posted (Estimate)

June 27, 2011

Study Record Updates

Last Update Posted (Actual)

May 25, 2021

Last Update Submitted That Met QC Criteria

May 1, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UASLP-PD001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

Each participant has to sign the concern form. We can share his clinical data, but not private information.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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