Introduction
Ample pre-clinical evidence points to neurotrophic factors (NTFs) as possible disease modifying therapies of Parkinson’s disease (PD). Glial cell-line derived neurotrophic factor (GDNF), neurturin (NTR) and cerebral dopamine neurotrophic factor (CDNF) convincingly demonstrate protection and restoration of nigrostriatal dopamine neurons by infusion of the NTFs or delivery of the corresponding genes into brain tissue in various experimental PD models [1]. GDNF, NRT and CDNF have also been studied in a limited number of phase I-II clinical studies but the outcomes have remained inconclusive [2]. GDNF protein and gene therapies show rather large interindividual variability among subjects which may at least partly mirror the status of the underlying disease pathology. In general, the subjects with advanced disease gain less benefit of the therapy when compared to subjects with shorter disease history.
Diagnosis of PD is based on the onset of motor symptoms which occur several years after the neurodegenerative process has started [3]. According to guidelines by Movement Disorders Society (MDS), the recognition of prodromal or early-phase PD relies on careful clinical observation and use of several biomarkers [4]. However, none of the biomarkers is specific or reliable enough to be used alone to predict the risk of PD, make an early diagnosis or follow the progression of the disease [5-7]. A reliable and discriminating prodromal biomarker would provide a temporal window during which putative disease-modifying therapies could be administered to halt or slow down the neuronal loss.
Several ongoing multicenter biomarker studies look for potential biomarkers that are collected longitudinally from a large cohort of early-stage PD patients and healthy controls using standardized data acquisition protocols [8, 9]. As an example, a Parkinson Progression Marker Initiative (PPMI) data-based study on the progression of PD shows promising results to monitor both motor and non-motor markers [10]. The currently available biomarker candidates can be grouped into biochemical biomarkers, imaging biomarkers and other biomarker modalities.