Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
J Neural Transm (Vienna). 2022 Sep;129(9):1133-1153. doi: 10.1007/s00702-022-02520-6. Epub 2022 Jun 13.
To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.
迄今为止，帕金森综合征的诊断基于临床检查。因此，当神经病理过程已经进展时，才会做出这些特定的诊断。然而，在明显的神经退行性变发生之前，疾病的修饰或神经保护被认为是最有效的。近年来，帕金森综合征的早期临床或前驱阶段成为了焦点。此外，不同疾病的亚型将更准确地预测个体疾病的进程。因此，患者将被纳入更具体的疾病实体和终点的临床试验中。此外，正在开发允许生化诊断的新型液体和成像生物标志物。这将导致未来更早的诊断和治疗。此外，治疗方法将更具体地考虑神经退行性帕金森综合征的潜在神经病理过程。具体而言，未来的治疗方法将针对易于聚集的蛋白质（如 alpha-synuclein 和 tau）的聚集、病理性聚集的降解以及病理性蛋白聚集在整个大脑中的传播。这些方法中的许多已经处于（临床前）开发阶段。此外，抗炎方法正在开发中。此外，药物再利用是缩短新药开发过程的可行方法。
