Emerging Immunotherapies for Parkinson Disease

Symptomatic treatment options for Parkinson disease have steadily improved, and individualized therapeutic approaches are becoming established for every stage of the disease. However, disease-modifying therapy with a causal approach is still unavailable. The central causative role of alpha-synuclein pathology, including its progressive spread to most areas of the CNS, has been widely recognized, and a strong involvement of immune responses has recently been discovered. New immunologic technologies have been shown to effectively prevent the progression of alpha-synuclein pathology in animal models. These approaches have recently been translated into the first human clinical trials, representing a novel starting point for the causal therapy of Parkinson disease. In this review, the pathomechanistic role of alpha-synuclein and its influence on the surrounding cellular environment are analyzed with a strong focus on immune responses and neuroinflammation. The potential of novel immunotherapeutic approaches that reduce the burden of alpha-synuclein pathology in the CNS is critically evaluated, and currently ongoing human clinical trials are presented. The clinical development of these new immunotherapies is progressing rapidly and gives reason to hope that a causal therapy of Parkinson disease could be possible in the foreseeable future.