This grant builds upon the research from a prior grant: Multimodal assessment of gastric motility in subjects at (pre)clinical stages of Parkinson´s Disease - A pathohistological and functional in-vivo-testing of Braak's pathoanatomical model
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.
Very similar to the results obtained in our pilot study, mean ghrelin concentrations (especially acyl-ghrelin concentrations) in healthy volunteers were higher compared to mean ghrelin concentrations in patients. PD patients and patients with idiopathic REM sleep behaviour disorder exhibited very similar mean ghrelin concentrations.
Due to a high inter-individual variability in ghrelin concentrations, the difference between patients and controls was not statistically significant.
Our data show that serum ghrelin concentrations do not qualify as PD biomarker due to a very high inter-individual variability. However, the difference in mean ghrelin serum concentrations between patients and controls indicates that ghrelin might be a relevant candidate for understanding PD-related changes in the neuroendocrine system, especially for understanding disturbances in the brain-gut-axis in PD. Further investigations are necessary to evaluate the role of ghrelin in PD and its therapeutic potential.
Presentations & Publications
Unger MM, Möller JC, Mankel K, Eggert KM, Bohne K, Bodden M, Stiasny-Kolster K, Kann PH, Mayer G, Tebbe JJ, Oertel WH. Postprandial ghrelin response is reduced in patients with Parkinson's disease and idiopathic REM sleep behaviour disorder: a peripheral biomarker for early Parkinson's disease? J Neurol. 2011 Jun;258(6):982-90. Epub 2010 Dec 24. PubMed PMID: 21181542.
Unger MM, Ekman R, Björklund AK, Karlsson G, Andersson C, Mankel K, Bohne K, Tebbe JJ, Stiasny-Kolster K, Möller JC, Mayer G, Kann, Oertel WH. Unimpaired postprandial pancreatic polypeptide secretion in Parkinson’s disease and REM sleep behaviour disorder. Mov Disord. in press
20th Annual Meeting of the German Society for Sleep Research and Sleep Medicine, December 2012, Berlin,Talk: Neuroendocrine peptides and REM sleep behaviour disorder