Research of Biomarkers in Parkinson Disease
Condition: Parkinson Disease; Multiple System Atrophy; Progressive Supranuclear Palsy; Huntington Disease; Dystonia; Diffuse Lewy Body Disease
MeSH terms: Parkinson Disease; Dystonia; Huntington Disease; Multiple System Atrophy; Shy-Drager Syndrome; Supranuclear Palsy, Progressive; Lewy Body Disease; Atrophy
Study type: Observational

Summary: 
      The main goal of the GENEPARK consortium is to employ innovative haemogenomic approaches to
      determine gene expression profiles specific for genetic and idiopathic Parkinson's disease
      (PD) patients. These gene expression signatures will be utilised clinically as non-invasive
      diagnostic tests for PD. The sensitivity of the newly developed diagnostic test will be
      determined by extensive validations on an independent cohort of PD patients, whereas the
      specificity will be assessed by testing patients with atypical parkinsonisms, including
      multiple system atrophy, progressive supranuclear palsy and diffuse Lewy body disease. In
      order to test the specificity of the diagnostic set in other disorders that affect basal
      ganglia, Huntington's disease and dopa responsive dystonia patients will be analysed. The
      second objective of the proposal is to determine correlations between gene expression
      signatures and different stages of PD and thus provide the basis for early diagnosis and
      monitoring of disease progression. These changes in blood gene expression will be correlated
      with alterations detected by neuroimaging in the brain of PD patients. Such combinations of
      molecular and morphological markers of disease may ultimately facilitate the selection and
      monitoring of neuroprotective therapies for PD. Finally, GENEPARK aims to develop new
      bioinformatic software tools for selection of genomic biomarkers using microarray data. A set
      of established computational tools will be applied and novel methods, some of them based on
      mechanistic modelling of the neurodegenerative diseases, will be developed in order to study
      the advantages and limitations of the different methodologies.

      With special emphasis on the careful clinical selection of patients and sufficient power
      regarding patient numbers, as well as extensive quality control and validation of the data,
      GENEPARK aims to develop a standardised approach to development and validation of
      haemogenomic biomarkers of disease.
    

Detailed description: 
      Employ innovative haemogenomic approaches to determine gene expression signatures specific
      for idiopathic Parkinson's disease (PD). There is currently no specific clinical or
      laboratory diagnostic test available for PD. In GENEPARK, blood samples from patients with
      genetic PD and idiopathic PD will be analysed by microarrays to identify gene expression
      signatures specific for PD. The specificity of the new biomarkers for PD will be tested by
      the analysis of patients with atypical parkinsonisms, including multiple system atrophy
      (MSA), progressive supranuclear palsy (PSP) and diffuse Lewy body disease (DLBD), as well as
      in patients with other basal ganglia disorders such as Huntington's disease (HD) and dopa
      responsive dystonia (DRD). The validated gene expression signatures will be utilised to
      develop a new test for diagnosis of idiopathic PD. Determine correlation between gene
      expression signatures and different stages of PD.

      Gene expression in presymptomatic and symptomatic patients with genetic forms of PD as well
      as patients in various stages of idiopathic PD will be analysed to identify gene expression
      signatures specific for various stages of the disease. It should be emphasised that since no
      clinical measures are present in presymptomatic genetic PD such molecular markers could serve
      as surrogate markers to monitor therapeutic efficacy of possible preventive treatments in PD.
      Determine correlations between gene expression signatures and morphological evidence of
      neurodegenerative process in PD brain as determined by neuroimaging. Gene expression
      signatures identified in blood samples will be correlated with changes in brain as detected
      by neuroimaging in PD patients. Such correlations of molecular and morphological markers of
      disease will facilitate the selection of blood markers in relation to disease progression.
      Moreover, molecular and morphological markers of disease progression could be utilised in
      combination for monitoring the effects of new neuroprotective therapies for PD. Develop
      standardised approaches to development and validation of haemogenomic biomarkers.

      This objective will be achieved by the special emphasis on careful clinical selection of
      patients, sufficient power regarding patient numbers, as well as extensive quality control
      and validation of the data. Develop new bioinformatic software tools for selection of genomic
      biomarkers using microarray data. The aim of the GENEPARK is to develop the theoretical
      foundations and to build the software tools for sample classification and selection of
      genomic biomarkers using microarray data. The established computational tools and novel
      methods developed within the GENEPARK will be applied to the patient data to study advantages
      and limitations of different methodologies.
    

Sampling method: Non-Probability Sample
Study population: 
        Patients with Parkinson's disease and related
      
Keywords: biomarkers; neuroimaging; genetics; PET; Genetic and Idiopathic Parkinson; Multiple Systemic Atrophy; Huntington; Dopa Responsive Dystonia