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
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View full resultsBasic Information
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COMPLETED
87 participants
OBSERVATIONAL
2011-02-28
2014-10-31
Brief Summary
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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.
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Detailed Description
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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
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Study Design
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CASE_CONTROL
CROSS_SECTIONAL
Study Groups
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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
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
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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.
Eligibility Criteria
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Inclusion Criteria
* Subject is a male or female between the age of 50 and 95
* Subject will write the informed consent
Exclusion Criteria
* Signs of cerebrovascular pathology
* Brain tumor
* Severe unrelated neurological or physical disease
35 Years
95 Years
ALL
Yes
Sponsors
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Universidad Autonoma de San Luis Potosí
OTHER
Responsible Party
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Ildefonso Rodriguez-Leyva
MD, PhD, FAAN, FANA
Principal Investigators
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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
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Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosí City, , Mexico
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Other Identifiers
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UASLP-PD001
Identifier Type: -
Identifier Source: org_study_id
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