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Neurotoxic Inflammatory Metabolites as Biomarkers of Disease Progression in Parkinson’s Disease

Study Rationale: Individuals with Parkinson’s disease (PD) have inflammation in the brain, cerebrospinal fluid and the blood. We think that inflammation drives the worsening of PD because it increases the production of neurotoxic metabolites called kynurenines. We discovered that a number of these compounds are increased in people with PD, and that their levels correlate with the severity of the disease. Now, we will validate that these compounds can be used as biomarkers of PD in another PD cohort. Ultimately, we expect to develop novel PD biomarkers and to target the kynurenine pathway for potential PD treatment.

Hypothesis: With this study we expect to confirm that neurotoxic compounds produced by the kynurenine pathway are linked to the worsening of PD.

Study Design: Using our established and optimized methods, we will measure the concentrations of compounds that reflect changes in the activity of the kynurenine pathway in the blood and cerebrospinal fluid of people with PD and healthy controls. We will then use statistical methods to determine the relationship between the levels of the compounds and the stage in disease progression for each individual. We will also determine whether the same amounts of these compounds are detected regardless of whether people are experiencing the acute effects of medication intake.

Impact on Diagnosis/Treatment of Parkinson’s disease: Our work could impact both the diagnosis and the treatment of PD. If our biomarkers are sufficiently accurate, they can be used to detect early cases of PD and assess the effects of new treatments. Moreover, available drugs that target the kynurenine pathway could be tested as novel PD treatments.

Next Steps for Development: The next step will be testing our biomarkers in a group of individuals with prodromal and early-stage PD, to determine whether they can be used to predict PD before clear motor symptoms appear.


Researchers

  • Lena Brundin, MD, PhD

    Grand Rapids, MI United States


  • Xuemei Huang, MD, PhD

    Hershey, PA United States


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