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

NCT ID: NCT01380899

Last Updated: 2021-05-25

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Total Enrollment

87 participants

Study Classification

OBSERVATIONAL

Study Start Date

2011-02-28

Study Completion Date

2014-10-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Parkinson Disease Parkinsonian Disorders

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

CASE_CONTROL

Study Time Perspective

CROSS_SECTIONAL

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

Biopsy of skin

Intervention Type PROCEDURE

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.

No interventions assigned to this group

Control group

Subjects without neurodegenerative disease and apparently good health status with an age that matches the problems groups

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type PROCEDURE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

35 Years

Maximum Eligible Age

95 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Universidad Autonoma de San Luis Potosí

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Ildefonso Rodriguez-Leyva

MD, PhD, FAAN, FANA

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Ildefonso Rodríguez-Leyva, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Central "Dr. Ignacio Morones Prieto"

Maria E Jimenez-Capdeville, PhD

Role: STUDY_DIRECTOR

Universidad Autonoma de San Luis Potosi

Juan P Castanedo-Cazares, MD

Role: STUDY_DIRECTOR

Hospital Dr. Ignacio Morones Prieto

Erika G Chi-Ahumada, MC

Role: STUDY_CHAIR

Facultad de Medicina, UASLP

Maria E Jimenez-Capdeville, PhD

Role: STUDY_CHAIR

Facultad de Medicina

Robert A. Norman, MD, PhD.

Role: STUDY_CHAIR

Independent Dermatologist

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Hospital Central Dr. Ignacio Morones Prieto

San Luis Potosí City, , Mexico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Mexico

References

Explore related publications, articles, or registry entries linked to this study.

Nutt JG, Wooten GF. Clinical practice. Diagnosis and initial management of Parkinson's disease. N Engl J Med. 2005 Sep 8;353(10):1021-7. doi: 10.1056/NEJMcp043908. No abstract available.

Reference Type BACKGROUND
PMID: 16148287 (View on PubMed)

Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson disease. Arch Neurol. 1999 Jan;56(1):33-9. doi: 10.1001/archneur.56.1.33.

Reference Type BACKGROUND
PMID: 9923759 (View on PubMed)

Hughes AJ, Daniel SE, Kilford L, Lees AJ. Accuracy of clinical diagnosis of idiopathic Parkinson's disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry. 1992 Mar;55(3):181-4. doi: 10.1136/jnnp.55.3.181.

Reference Type BACKGROUND
PMID: 1564476 (View on PubMed)

Tuite PJ, Krawczewski K. Parkinsonism: a review-of-systems approach to diagnosis. Semin Neurol. 2007 Apr;27(2):113-22. doi: 10.1055/s-2007-971174.

Reference Type BACKGROUND
PMID: 17390256 (View on PubMed)

Ibanez-Salazar A, Banuelos-Hernandez B, Rodriguez-Leyva I, Chi-Ahumada E, Monreal-Escalante E, Jimenez-Capdeville ME, Rosales-Mendoza S. Oxidative Stress Modifies the Levels and Phosphorylation State of Tau Protein in Human Fibroblasts. Front Neurosci. 2017 Sep 7;11:495. doi: 10.3389/fnins.2017.00495. eCollection 2017.

Reference Type BACKGROUND
PMID: 28936161 (View on PubMed)

Rodriguez-Leyva I, Calderon-Garciduenas AL, Jimenez-Capdeville ME, Renteria-Palomo AA, Hernandez-Rodriguez HG, Valdes-Rodriguez R, Fuentes-Ahumada C, Torres-Alvarez B, Sepulveda-Saavedra J, Soto-Dominguez A, Santoyo ME, Rodriguez-Moreno JI, Castanedo-Cazares JP. alpha-Synuclein inclusions in the skin of Parkinson's disease and parkinsonism. Ann Clin Transl Neurol. 2014 Jul;1(7):471-8. doi: 10.1002/acn3.78. Epub 2014 Jul 1.

Reference Type RESULT
PMID: 25356418 (View on PubMed)

Rodriguez-Leyva I, Chi-Ahumada EG, Carrizales J, Rodriguez-Violante M, Velazquez-Osuna S, Medina-Mier V, Martel-Gallegos MG, Zarazua S, Enriquez-Macias L, Castro A, Calderon-Garciduenas AL, Jimenez-Capdeville ME. Parkinson disease and progressive supranuclear palsy: protein expression in skin. Ann Clin Transl Neurol. 2016 Feb 1;3(3):191-9. doi: 10.1002/acn3.285. eCollection 2016 Mar.

Reference Type RESULT
PMID: 27042679 (View on PubMed)

Rodriguez-Leyva I, Chi-Ahumada E, Mejia M, Castanedo-Cazares JP, Eng W, Saikaly SK, Carrizales J, Levine TD, Norman RA, Jimenez-Capdeville ME. The Presence of Alpha-Synuclein in Skin from Melanoma and Patients with Parkinson's Disease. Mov Disord Clin Pract. 2017 Jun 1;4(5):724-732. doi: 10.1002/mdc3.12494. eCollection 2017 Sep-Oct.

Reference Type RESULT
PMID: 30363411 (View on PubMed)

Mejia M, Rodriguez-Leyva I, Cortes-Enriquez F, Chi-Ahumada E, Portales-Perez DP, Macias-Islas MA, Jimenez-Capdeville ME. Low levels of alpha-synuclein in peripheral tissues are related to clinical relapse in relapsing-remitting multiple sclerosis: a pilot cross-sectional study. J Neurol Sci. 2019 Jan 15;396:87-93. doi: 10.1016/j.jns.2018.11.003. Epub 2018 Nov 3.

Reference Type RESULT
PMID: 30445232 (View on PubMed)

Jimenez-Capdeville ME, Chi-Ahumada E, Garcia-Ortega F, Castanedo-Cazares JP, Norman R, Rodriguez-Leyva I. Nuclear Alpha-Synuclein in Parkinson's Disease and the Malignant Transformation in Melanoma. Neurol Res Int. 2025 Jan 6;2025:1119424. doi: 10.1155/nri/1119424. eCollection 2025.

Reference Type DERIVED
PMID: 39816956 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

UASLP-PD001

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.