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Funded Studies

Analysis of the enteric nervous system using routine colonic biopsies: a biomarker of neurodegeneration in Parkinson's Disease?

Objective/Rationale
The “core” of the neuronal lesions of Parkinson’s disease (PD) is the progressive degeneration of dopamine neurons in the central nervous system (CNS). It is now well established that PD lesions occur outside the CNS and, in particular, in the “neurons of the gut”, namely the enteric nervous system (ENS). Some recent studies have suggested that the alteration of the ENS could be a key and early step in the pathological process leading to neurodegeneration of the CNS. We have recently shown that the ENS was readily analyzable using routine biopsies obtained by colonoscopy suggesting that the ENS could represent a window toward neurodegeneration of the CNS in living patients. The aim of our project is to develop an original biomarker for PD, based upon the detection of pathological changes in routine colonoscopic biopsies of PD patients.
Project Description
In order to determine whether colonic biopsies may indeed be a reliable biomarker for PD, the colonic biopsies of 30 PD patients (Enteropark study ClinicalTrials.gov identifier: NCT00491062) will be compared to the biopsies of 10 control patients and 5 patients with multiple system atrophy (a parkinsonian syndrome which is a common differential diagnosis of PD). The biopsies will be analyzed in our laboratory using specific staining for the pathological inclusions found in PD. The severity of the pathological burden in PD patients will be compared to the severity of both motor and digestive symptoms.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:  
The relevance for developing such a biomarker is two-fold:

  • the analysis of the enteric neurons using routine colonic biopsies could represent a marker of the severity of the disease in PD patients (biomarker for disease severity)
  • the analysis of the enteric neurons using colonic biopsies could enable us to distinguish between PD and other parkinsonian syndromes such as multiple system atrophy (biomarker for differential diagnosis)

Anticipated Outcome
The impact of the biomarker we are seeking to develop is potentially major, because (1) provided the enteric synucleinopathy is specific for PD, it opens the way to a neuropathological diagnosis in the living patient; (2) according to recent data supporting the precocious involvement of the enteric nervous system (ENS), it may constitute a preclinical biomarker.

Final Outcome

The goal of this study was to measure alpha-synuclein levels in colonic biopsy tissue in PD and control subjects. Alpha-synuclein pathology was found in 21/29 PD patients but 0/10 control subjects. More work is needed to determine the reliability and specificity of the findings and determine whether these observations also occur in subjects with Multiple Systems Atrophy (MSA).

Publication Based on MJFF Funding:
Lebouvier T, Neunlist M, Bruley des Varannes S, Coron E, Drouard A, N’Guyen JM, Chaumette T, Tasselli M, Paillusson S, Flamand M, Galmiche JP, Damier P, Derkinderen P. Colonic biopsies to assess the neuropathology of Parkinson’s disease and its relationships with symptoms. PLoS One. 2010 Sep 14;5(9):e12728
Thibaud Lebouvier, Maddalena Tasselli, Sébastien Paillusson, Hélène Pouclet, Michel Neunlist and Pascal Derkinderen. Biopsable neural tissues: toward new biomarkers for Parkinson’s disease? Front. Psychiatry doi: 10.3389/fpsyt.2010.00128
 


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