aPD（進行期Parkinson病）の治療戦略

抄録

Advanced Parkinson disease (aPD) leads to a decline in activities of daily living (ADL) and quality of life (QOL) due to worsening motor and non–motor symptoms, making it difficult to manage with conventional oral medication alone. In particular, the narrowing of the therapeutic window of levodopa results in wearing–off and dyskinesia, causing fluctuations in symptoms. This narrowing is attributed to dopaminergic neuronal degeneration, reduced presynaptic dopamine storage capacity, a short half–life of levodopa, and postsynaptic plasticity changes. Wearing–off occurs due to decreased levodopa plasma levels, leading to symptom worsening, while dyskinesia appears at peak–dose or during transitions between ON and OFF states, significantly impairing motor function.

To address these issues, pharmacological strategies aim to stabilize levodopa plasma levels through the use of COMT inhibitors, MAO–B inhibitors, and dopamine receptor agonists. In particular, adjunctive therapy with opicapone has been shown to extend the half–life of levodopa and stabilize its plasma concentration. Furthermore, for patients meeting the Delphi Panel Approach 5–2–1 criteria, device–aided therapy (DAT) is indicated, with options including subthalamic nucleus deep brain stimulation (STN–DBS), levodopa–carbidopa intestinal gel infusion (LCIG), and continuous subcutaneous infusion of foslevodopa–foscarbidopa. STN–DBS is superior in reducing dyskinesia and lowering the levodopa equivalent daily dose (LEDD), while LCIG provides stable drug delivery but has a higher risk of device–related complications. Treatment selection should be personalized based on the patient's disease state and lifestyle, and the appropriate combination of pharmacological and device–aided therapies is essential for symptom stabilization and improving QOL.