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.