Regarding a-synuclein toxicity, multiple processes may be involved, including protein synthesis, mis-folding, fibril formation and aggregation, degradation, and cell-to-cell transmission. Therefore, several approaches targeting α-synuclein in PD patients have been proposed [60]. Several studies have evaluated the effects of monoclonal antibodies directed to different parts of the a-synuclein protein (N-, mid-, C-terminal, or full-length peptide). Therefore, various human clinical trials using anti-a-synuclein antibodies have been performed showing a good safety profile and tolerability, and a serum reduction of free a-synuclein levels and increased free plus antibody-bound levels has been reported [248]. Two phase 2 RCT are ongoing (RO7046015, the PASADENA trial and BIIB054, the SPARK trial) [245].