Slowing Parkinson's Disease Progression with Vaccination and Other Immunotherapies

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. There are several recognized pathways leading up to dopaminergic neuron loss in the substantia nigra pars compacta and other cells in the brain as a result of age-related, genetic, environmental, and other processes. Of these, the most prominent is the role played by the protein α-synuclein, which aggregates and is the primary component of Lewy bodies, the histopathological hallmark of PD. The latest disease-modifying treatment options being investigated in PD are active and passive immunization against α-synuclein. There are currently five different monoclonal antibodies investigated as passive immunization and three drugs being studied as active immunization modalities in PD. These work through different mechanisms but with a common goal-to minimize or prevent α-synuclein-driven neurotoxicity by reducing α-synuclein synthesis, increasing α-synuclein degradation, and preventing aggregation and propagation from cell to cell. These promising strategies, along with other potential therapies, may favorably alter disease progression in PD.