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Prospective Validation of Risk Markers for the Development of Parkinson’s Disease

The development of disease-course modifying or neuroprotective treatments is still an unmet therapeutical need in Parkinson’s disease. Treatment will likely work best if initiated as early as possible. There is ample evidence to suggest that PD is present in “latent” or “preclinical” form many years before the onset of classical motor symptoms. The current project is aimed to validate a novel, putative risk marker for PD found in up to 10 % of the healthy population. In addition, a battery of so-called “pre-motor markers” will also be assessed in a large cohort of healthy subjects with respect to their predictive values regarding the risk to develop signs and symptoms of PD.
Project Description:
Transcranial sonography (TCS) is an easy-to-administer, safe and non-invasive established neurological assessment modality. The groups of Drs. Becker and Berg in Germany were the first to point out in the mid-1990’s that this investigation reveals characteristic changes in ultrasound echogenicity in the area of the substantia nigra in PD. Current evidence suggest that this ultrasound marker may be detectable years before onset of classical motor symptoms of PD. At the Universities of Tübingen, Innsbruck and Homburg more than 1800 healthy subjects older than 50 years were examined with respect to SN echogenicity and epidemiologic risk factors as well as premotor markers like depression, autonomic and smelling dysfunction, neuropsychologcial deficits and slight motor signs 2.5 years ago. With support of MJFF, all subjects will now be reassed to detect a possible development of motor symptoms and therewith evaluate the predictive value of SN hpyerechogenicity and the premotor markers concerning the possible development of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If conclusive, TCS will be established with this large study as a first reliable and broadly applicable screening instrument for a vulnerability to PD. Moreover, this study will provide a battery of reliable premotor signs as additional biomarkers to better identify subjects at risk for PD within the cohort of subjects. Therefore, the results of this study will open up the possibility to test for the first time "neuropreventive" strategies in PD based on their ability to delay the onset of clinical illness in properly defined at-risk subjects. Such trials, if positive, will mark a major breakthrough in the current therapeutic approach to this second most common neurodegenerative disorder.
Anticipated Outcome:
According to the incidence of PD, the study team expects 10-12 of the healthy subjects to have developped PD over the last 2.5 years. They are anticipated to have hyperechogenicity of the SN and a certain, yet unknwon, combination of premotor markers. If this hypothesis holds true, a defined battery to test the risk for PD before motor manifestation of the disease may be at hand, allowing the development and implementation of strategies for earlier neuroprotective intervention.


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