The development of a disease-modifying therapy that delays, reverses or stops the symptom
progression remains the most important unmet goal in the treatment of Parkinson's disease
(PD). Apart from its glucose lowering effect, glucagon-like peptide-1 (GLP-1) receptor
stimulation has been investigated in animal models of PD and shown to increase neurogenesis,
to arrest and possible reverse nigrostriatal damage, and to protect dopaminergic neurons from
neurodegeneration. Exenatide is a synthetic analogue of human GLP-1, resistant to the
metabolic processes that degrade it in its naturally occurring form. Results from a recent
randomised, double-blind, placebo-controlled trial in PD showed that patients in active
treatment for one year were improved compared to the placebo arm with regard to their
performance in Movement Disorders Society - Unified Parkinson's Disease Rating Scale
(MDS-UPDRS) motor subscale in the practically defined OFF medication state.
The aim of this trial is to investigate the effect of Exenatide, 2 mg, subcutaneous
injection, once weekly on disease progression represented by the change in longitudinal
Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro- D-glucose (FDG-PET) in
individual PD subjects, and to identify an Exenatide-related pattern in FDG-PET that will
provide insight into the treatment-effect in the brain. The investigators chose the standard
regimen prescribed in Type 2 Diabetes Mellitus (T2DM) and the regimen used in a recent trial
in PD. The treatment period will be 18 months, and patients will be randomly assigned to
either active treatment or placebo. Patients with PD diagnosis, stable on medication during
the last year, and Hoehn and Yahr stage 2 or less will be evaluated for the inclusion.