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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01380899
Recruitment Status : Completed
First Posted : June 27, 2011
Results First Posted : May 25, 2021
Last Update Posted : May 25, 2021
Information provided by (Responsible Party):
Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí

Tracking Information
First Submitted Date June 17, 2011
First Posted Date June 27, 2011
Results First Submitted Date November 4, 2020
Results First Posted Date May 25, 2021
Last Update Posted Date May 25, 2021
Study Start Date February 2011
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: May 1, 2021)
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.
Original Primary Outcome Measures
 (submitted: June 23, 2011)
Fraction area of Alpha synuclein expression determined by immunohistochemistry in skin from patients with Parkinson disease and Parkinson Plus Syndromes, as a measure of selectively differentiate these two conditions. [ Time Frame: From date of clinical evaluation until the date of final report, assessed up to six months. ]
Alpha synuclein will be analysed by means of immunohistochemistry in skin samples of patients with Parkinson syndrome contrasted to patients with Parkinson Plus Syndromes, as a possible marker to differentiate between them.
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.
Official Title Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.
Brief Summary

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.

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
Study Design Observational Model: Case-Control
Time Perspective: Cross-Sectional
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA

We are obtaining the skin of the participants, by biopsy using a punch 3-4 mm in retro auricular area.

We are taking from affected subjects and his or her partner (the most husband or wife).

Sampling Method Non-Probability Sample
Study Population The patients will be selected from the department of neurology and the office of the principal investigator.
  • Parkinson Disease
  • Parkinsonian Disorders
Intervention 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.
Study Groups/Cohorts
  • 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.
    Intervention: Procedure: Biopsy of skin
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: May 1, 2021)
Original Estimated Enrollment
 (submitted: June 23, 2011)
Actual Study Completion Date October 2014
Actual Primary Completion Date October 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sexes Eligible for Study: All
Ages 35 Years to 95 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Mexico
Removed Location Countries  
Administrative Information
NCT Number NCT01380899
Other Study ID Numbers UASLP-PD001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: Each participant has to sign the concern form. We can share his clinical data, but not private information.
Responsible Party Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí
Study Sponsor Universidad Autonoma de San Luis Potosí
Collaborators Not Provided
Principal Investigator: Ildefonso Rodríguez-Leyva, MD Hospital Central "Dr. Ignacio Morones Prieto"
Study Director: Maria E Jimenez-Capdeville, PhD Universidad Autonoma de San Luis Potosi
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
PRS Account Universidad Autonoma de San Luis Potosí
Verification Date May 2021