Abstract
BackgroundThis study focuses on genetically stratified subgroups of Parkinson’s disease patients (PD) with an enrichment of risk variants in mitochondrial genes,who might benefit from treatment with the “mitochondrial enhancer” coenzyme Q10 (156 mg coenzyme Q10/d [QuinoMit Q10® Fluid] over six months). The study will be performed in a double-blind, randomized, and placebo-controlled parallel group manner.MethodsPD patients will be specifically identified and assigned to treatment groups stratified by their genetic “mitochondrial risk burden” and consequently expected mitochondrial dysfunction and treatment response to coenzyme Q10 (homozygous or compound heterozygous Parkin/PINK1 mutation carriers [P++], heterozygous Parkin/PINK1 mutation carriers [P+], “omics” positive [omics+], and “omics” negative PD patients [omics-]). The primary endpoint is the change in motor symptoms over six months (as measured by the change in the motor subscore of the MDS-UPDRS). Secondary clinical endpoints include motor fluctuations, non-motor symptoms, results of magnetic resonance imaging of brain energy metabolism (31P-magnetic resonance spectroscopy imaging), and changes in structural and functional brain anatomy (MRI).PerspectiveThis study may be a first step towards a successful prediction of treatment response based on the genetic status of PD patients and translate progress in molecular genetics into personalized patient care. Further, magnetic resonance spectroscopy imaging may help quantify increased energy supply objectively and within a brief time after the start of treatment. Therefore, the potential of MRSI also for other studies addressing brain energy metabolism may will be assessed.Trial registrationThis study was registered at the German Clinical Trial Registry (DRKS, DRKS00015880) on November 15th, 2018.
Highlights
This study focuses on genetically stratified subgroups of Parkinson’s disease patients (PD) with an enrichment of risk variants in mitochondrial genes,who might benefit from treatment with the “mitochondrial enhancer” coenzyme Q10 (156 mg coenzyme Q10/d [QuinoMit Q10® Fluid] over six months)
Despite rapid advances in Parkinson’s disease (PD) research, in particular in the elucidation of etiologic contributions, no disease-modifying therapy has become available to date, and the translation of these advances into improvements in patient care has proven challenging [9]
Since the discovery of the first monogenic forms, it is commonly known that PD is etiologically heterogeneous [1], and there is no doubt that both genetic and environmental factors contribute to the multifactorial genesis
Summary
Aim of the trial The current understanding of the genetic etiology of PD will be used to identify individual patients who would most likely benefit from the aforementioned specific therapy. Patients with a risk score between − 0.30 and + 0.30 do not belong to one of the two “extreme” omics groups These patients are not included in the study if they are not heterozygous, homozygous or compound heterozygous for mutations in the Parkin or PINK1 gene. If this proof-ofprinciple study is successful, future questions will address whether a potential benefit is sustained and whether the improvement is a mere symptomatic effect associated with improved energy metabolism or due to neuroprotective actions It would be of great interest to see whether the proposed omics-score helps to stratify PD patients or whether further improvements are needed to identify mitochondrial subgroups of PD patients (e.g., by selection/combination of other SNPs or functional assays) to impact more significantly on PD patient care.
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