Department of Neurology, University San Raffaele, Rome, Italy.
Deptartment of Neurology, Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy.
Nat Rev Neurol. 2024 Dec;20(12):695-707. doi: 10.1038/s41582-024-01034-x. Epub 2024 Nov 4.
Parkinson disease (PD) is the fastest growing neurological disorder globally and poses substantial management challenges owing to progressive disability, emergence of levodopa-resistant symptoms, and treatment-related complications. In this Review, we examine the current state of research into PD therapies and outline future priorities for advancing our understanding and treatment of the disease. We identify two main research priorities for the coming years: first, slowing the progression of the disease through the integration of sensitive biomarkers and targeted biological therapies, and second, enhancing existing symptomatic treatments, encompassing surgical and infusion therapies, with the goal of postponing complications and improving long-term patient management. The path towards disease modification is impeded by the multifaceted pathophysiology and diverse mechanisms underlying PD. Ongoing studies are directed at α-synuclein aggregation, complemented by efforts to address specific pathways associated with the less common genetic forms of the disease. The success of these efforts relies on establishing robust end points, incorporating technology, and identifying reliable biomarkers for early diagnosis and continuous monitoring of disease progression. In the context of symptomatic treatment, the focus should shift towards refining existing approaches and fostering the development of novel therapeutic strategies that target levodopa-resistant symptoms and clinical manifestations that substantially impair quality of life.
帕金森病（PD）是全球增长最快的神经退行性疾病，由于进行性残疾、出现对左旋多巴耐药的症状以及与治疗相关的并发症，给疾病管理带来了巨大挑战。在这篇综述中，我们研究了 PD 治疗方法的现有研究状况，并概述了推进我们对该疾病的认识和治疗的未来优先事项。我们确定了未来几年的两个主要研究重点：首先，通过整合敏感的生物标志物和靶向生物疗法来减缓疾病的进展；其次，通过手术和输注疗法等现有对症治疗，提高治疗水平，以推迟并发症的发生，改善长期患者管理。疾病修饰的道路受到 PD 多方面的病理生理学和不同机制的阻碍。正在进行的研究针对α-突触核蛋白聚集，并辅以努力解决与该疾病较不常见遗传形式相关的特定途径。这些努力的成功依赖于建立可靠的终点，结合技术，并确定可靠的生物标志物，用于早期诊断和持续监测疾病进展。在对症治疗方面，重点应转向完善现有的治疗方法，并促进开发针对左旋多巴耐药症状和严重影响生活质量的临床表现的新型治疗策略。
