Parkinson disease therapy: current strategies and future research priorities

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 alpha-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.Parkinson disease (PD) poses substantial management challenges owing to progressive disability and emergence of levodopa-resistant symptoms and treatment-related complications. This Review examines the current state of research into symptomatic and disease-modifying PD therapies and outlines future priorities for advancing our understanding and treatment of the disease.Parkinson disease (PD) is the fastest growing neurological disorder globally but, currently, no therapeutic intervention can modify disease progression and treatment is still based on levodopa (either alone or in combination with dopamine agonists or monoamine oxidase B or catechol--methyltransferase inhibitors) and device-aided therapies.Disease-modifying therapies targeting alpha-synuclein that are under investigation include active and passive immunization and small molecules that can inhibit protein aggregation.Studies of compounds that can enhance glucocerebrosidase activity, reduce leucine-rich repeat kinase 2 activity or prevent inflammation are ongoing or starting.Medications that can alleviate symptomatic manifestations, including new levodopa formulations, dopamine agonists with different dopamine receptor stimulation profiles or modes of administration, and gene and cell transplantation therapies, are under investigation.Early detection of PD is crucial, and educational programmes aimed at the general population could aid this effort by increasing awareness of the early symptoms.Biomarker discovery and validation initially require considerable financial and human resources, but the development of safe, easy-to-perform biomarker assays - for example, using blood samples or skin biopsies - would allow screening of large cohorts in a cost-effective manner.