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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

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.

Condition or disease Intervention/treatment
Parkinson Disease Parkinsonian Disorders Procedure: Biopsy of skin

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.

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Study Type : Observational
Actual Enrollment : 87 participants
Observational Model: Case-Control
Time Perspective: Cross-Sectional
Official Title: Usefulness of α-synuclein as a Marker for Early Diagnosis of Parkinson's Disease in Skin Biopsy.
Study Start Date : February 2011
Actual Primary Completion Date : October 2014
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. 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.

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).

Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 95 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
The patients will be selected from the department of neurology and the office of the principal investigator.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01380899

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Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosi, Mexico, 78290
Sponsors and Collaborators
Universidad Autonoma de San Luis Potosí
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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
Publications of Results:

Other Publications:
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Responsible Party: Ildefonso Rodriguez-Leyva, MD, PhD, FAAN, FANA, Universidad Autonoma de San Luis Potosí Identifier: NCT01380899    
Other Study ID Numbers: UASLP-PD001
First Posted: June 27, 2011    Key Record Dates
Results First Posted: May 25, 2021
Last Update Posted: May 25, 2021
Last Verified: May 2021
Individual Participant Data (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.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ildefonso Rodriguez-Leyva, Universidad Autonoma de San Luis Potosí:
Parkinson Disease
Parkinsonian Disorders
Lewy Bodies
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases