Influence of Inflammatory Profiles on PD Phenotype and Progression

01.06.2018 bis 31.12.2019

Study Rationale:
The clinical presentation of PD is highly variable, suggesting a strong influence of genetic and/or non-genetic modifying factors. In this context, inflammation is a potential candidate inducing clinical subtypes. A growing number of epidemiological and genetic studies as well as post-mortem and biomarker analyses provide evidence for a relevant role of inflammation in PD pathogenesis. However, at this point it is unclear whether inflammatory processes relate only to a specific subgroup of patients and whether they are primarily disease-causing or rather disease-maintaining and associated with disease progression.

Hypothesis:
We propose that inflammatory profiles can be defined through genetic and biochemical analyses, and that they predispose to different PD subtypes and rates of disease progression.

Study Design:
The present study includes two cohorts: 300 PD patients as well as 100 healthy control individuals. All participants will be genotyped and stratified according to the individual “genetic inflammatory burden”. Additionally, we will measure levels of inflammatory markers in blood (serum) and CSF from all of these individuals and analyze these in relation to the clinical phenotype and disease progression.
This allows (I) to differentiate PD-disease-specific findings from age-related effects and (II) to assess the predictive value of specific inflammatory candidates (alone or in concert) for phenotypical subtypes and disease progression in PD.

Impact on Diagnosis/Treatment of Parkinson’s disease:
If there are indeed inflammatory-driven PD subtypes, individuals presenting with a prominent inflammatory profile will be prime candidates for interventional studies with anti-inflammatory/immune modulating therapeutics, which would be an important step towards personalized medicine based on pathophysiological stratification.

Next Steps for Development:
Results of this study may be the basis for a pathway-specific clinical trial with established anti-inflammatory compounds as a disease-modifying treatment in PD.