Immunotherapy in Parkinson's disease: Current status and future directions.

Immunotherapeutic approaches for the treatment of Parkinson's disease (PD) and related synucleinopathies have steadily developed over the last two decades with several iterations currently being tested in clinical trials. Although classically characterized as a movement disorder, PD is also defined clinically by numerous non-motor features that can precede the motor manifestations and span across several decades of disease progression. Pathologically, PD is characterized by proteinaceous inclusions that largely consist of misfolded and aggregated forms of the protein, alpha-synuclein. Recent research has proposed that alpha-synuclein pathology is capable of propagating from cell-to-cell, and thus, may cause the clinical progression of the disease. Antibody-based therapies are ideal drugs to theoretically target pathological proteins, especially those located in the extracellular space. Several other targeting strategies have been developed to indirectly mitigate the propagation of alpha-synuclein and are in various stages of pre-clinical and clinical development. In this review, we discuss the current status of development for immunotherapies in PD as well as the primary challenges that must be hurdled to bring an effective immunotherapeutic drug to market.