The use of Vitamine K2 in Parkinson’s Disease patients with mitochondrial dysfunction

Project Description:

In spite of rapid advances in the field of Parkinson`s Disease (PD) research, and in particular in the elucidation of etiologic contributions, no disease-modifying therapy has become available to date. Thus, the translation of these advances into improvements in patient care has proven challenging. This is likely due to the fact that PD is a heterogeneous disorder, although genetic subtypes are particularly well defined (Domingo & Klein, 2018). Furthermore, personalized medicine approaches by means of gene-specific therapeutic strategies have recently emerged. As an example, glycosylceramid synthase inhibitors in GBA-linked PD to reduce the concentration of glycosylceramid and thus to reduce the propensity to develop PD-typical pathology (Schapira, 2015). In this study, we will investigate potential effects of a vitamin K2 supplementation for one week in a subgroup of PD patients that is characterized by mitochondrial dysfunction. Vitamin K2 is of particular interest, because it exerts specific effects in its role as an electron carrier in the respiratory chain of mitochondria. Mitochondrial impairment has been well demonstrated in patients with either homozygous or compound-heterozygous PINK1 or Parkin mutations (Exner, Lutz, Haass, & Winklhofer, 2012). If drugs targeting mitochondrial dysfunction are tested in unselected PD patients (i.e. those without critical impairment of mitochondrial function), patients may not benefit, thus diluting any effect observed. Therefore, we aim to test groups of homozygous or compound-heterozygous PINK1/Parkin mutation carriers, matched non-genetic PD patients, and healthy controls, which should reveal notable differences in the load of mitochondrial impairment and subsequent energy metabolism. The proposed project is placed directly at the intersection of metabolism and higher brain (dys-)function. Further methods, e.g., as provided by the Metabolic Core Unit, will also be applied to correct our findings for body composition and other potential influencing factors.

Research Aims:

Using a placebo-controlled, parallel group study design, the following research questions will be addressed:

• Do patients with mitochondrial PD have improved energy levels after one week of vitamin K2 supplementation as measured by 31P-MRSI?
• Do both non-genetic PD patients and healthy controls show an increase in brain energy levels after one week of vitamin K2 supplementation
• Do other neuroimaging- or omics-approaches predict individual treatment response to one week of vitamin K2 supplementation in non-genetic PD patients?