Despite many clinical trials over the last three decades, the goal of demonstrating that a treatment slows the progression of Parkinson’s disease (PD) remains elusive. Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. Here we review recent and ongoing clinical trials employing novel strategies toward disease modification, including those targeting alpha-synuclein and those repurposing drugs approved for other indications. Active and passive immunotherapy approaches are being studied with the goal to modify the spread of alpha-synuclein pathology in the brain. Classes of currently available drugs that have been proposed to have potential disease-modifying effects for PD include calcium channel blockers, antioxidants, anti-inflammatory agents, iron-chelating agents, glucagon-like peptide 1 agonists, and cAbl tyrosine kinase inhibitors. The mechanistic diversity of these treatments offers hope, but to date, results from these trials have been disappointing. Nevertheless, they provide useful lessons in guiding future therapeutic development.

尽管过去三十年进行了许多临床试验，但证明治疗方法可以减缓帕金森病 (PD) 进展的目标仍然难以实现。研究进展为帕金森病发病机制的细胞通路提供了新的见解，并提供了越来越引人注目的治疗靶点。在这里，我们回顾了最近和正在进行的临床试验，这些试验采用了疾病修饰的新策略，包括针对 α-突触核蛋白的试验和那些批准用于其他适应症的药物的再利用。主动和被动免疫治疗方法正在研究中，目的是改变α-突触核蛋白病理学在大脑中的传播。目前已提出对 PD 具有潜在疾病缓解作用的药物类别包括钙通道阻滞剂、抗氧化剂、抗炎剂、铁螯合剂、胰高血糖素样肽 1 激动剂和 cAbl 酪氨酸激酶抑制剂。这些治疗方法的机制多样性带来了希望，但迄今为止，这些试验的结果令人失望。尽管如此，它们为指导未来的治疗发展提供了有用的经验教训。