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Trace Amines and Their Metabolites as Potential Heraldic Markers in Parkinson’s Disease

Objective/Rationale:
Tools for early and unambiguous diagnosis of PD are currently missing and disease symptoms are easily mistaken. On the other hand, prompt recognition of PD subjects may increase the chances of therapeutic success. Our preliminary evidence that the level of a trace amine, octopamine, is altered in early PD provides new hopes for better diagnosis and therapy. Our aim is to investigate disease-related fluctuations in octopamine and similar compounds in early diagnosed and advanced PD patients.

Project Description:
Both early and advanced PD patients will be evaluated by measuring, in blood, trace amines and related compounds by high performance liquid chromatography (HPLC). This technique enables for identification and quantification of single molecules from complex mixtures such as biologic fluids. “Early PD patients” will consist of subjects who were recently diagnosed and did not receive any treatment yet. As response to pharmacological treatment is variable, advanced patients with different responsiveness to therapy will be selected. PD patients will be compared with healthy subjects of correspondent ages. The results will be analyzed to verify correlations between trace amine levels and disease severity as well as differential response to therapy.

Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The demonstration of decreased trace amine levels in early PD patients will prompt the development of new diagnostic tests that will be applicable in cases of suspect PD as well as to predict responsiveness to therapy. Proving that these changes are specific, early (possibly pre-symptomatic) alterations will have a dual clinical impact: First, it will minimize the risk of wrong diagnosis; second, it will allow for early therapy assignment, thereby increasing the chances of clinical success.

Anticipated Outcome:
In preliminary studies we found decreased octopamine levels in PD patients, especially at a stage in which other known signs of disease, (e.g. reduced noradrenaline), are not yet present. Moreover, octopamine level was restored by therapy. This suggests that changes in octopamine and, possibly, other related compounds may be an index of incoming disease. We expect a systematic and larger-scale analysis in patients to confirm (and/or reveal new) disease-related changes of diagnostic and clinical utility.

Progress Report

Interim Progress Report: Previous research has suggested that the level of specific chemical compounds, the so-called “trace amines,” can be a marker for early and, possibly, oncoming Parkinson’s disease. This project intends to establish the relevance of these compounds as clinically-relevant biomarkers in the blood of patients at different disease stages (i.e. early diagnosed and advanced). The study involves three different clinical centers in Italy and employs novel metabolomic technologies. At present, approximately half of the total planned samples have been collected and preliminary results are soon expected.


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