Ghrelin - a Peripheral, Preclinical Biomarker for Parkinson's Disease

Promising Outcomes of Original Grant:
In our original grant we investigated serum concentrations of the hormone ghrelin in the fasting state and at different time points after a standardized test meal. We found that the course of ghrelin serum concentrations (after the test meal) was different between healthy controls and PD patients as well as between healthy controls and patients with REM sleep behavior disorder (RBD) - a sleep disorder that confers a high risk to develop PD.

Objectives for Supplemental Investigation: 
Based on our initial data we concluded that the dynamic regulation of ghrelin excretion is impaired in patients PD and in RBD and that ghrelin might be suitable as an early peripheral biomarker for PD.

The objectives of the present study are
1) to reproduce the initial finding of our pilot study in a second, larger sample.
2) to determine the PD-specificity of our initial finding by including two additional control cohorts, i.e. patients with diabetes mellitus type 2 and multiple sclerosis. For both conditions, ghrelin serum concentrations different from healthy controls have been described. However, it is still unknown whether the dynamic regulation of ghrelin in these patients is disturbed in the same way as in RBD and PD patients.
3) to determine which subform of the hormone ghrelin (acyl-ghrlein or desacyl-ghrelin) is responsible for the disturbed ghrelin response we found in our initial study.

Importance of This Research for the Development of a New PD Therapy: 
Other groups have shown that in a pre-clinical model of toxin-induced Parkinson’s disease, administration of ghrelin has a neuroprotective potential. In addition, it is known that ghrelin acts on systems that frequently are also affected in PD (gastro-intestinal tract, mood, cognition, sleep, etc.). Proof of an early disturbance in the ghrelin system (evolving) PD might therefore be of future diagnostic and also potential therapeutic value.