Advanced Therapeutics in Parkinson's Disease: What's New?

PURPOSE OF REVIEW: To provide a concise, clinically oriented update on advanced therapies for Parkinson’s disease. RECENT FINDINGS: Subcutaneous infusion of foscarbidopa/foslevodopa and apomorphine reduce OFF time and improve “good ON time”, though infusion site reactions remain of some concern. Image-guided programming may shorten programming time while matching motor outcomes; while adaptive/closed-loop deep brain stimulation using local field potential signals may improve symptoms and quality of life with a lower energy use. Remote programming accelerates clinical benefit and expands access. Approved magnetic resonance guided high intensity focused ultrasound targets now include the ventralis intermediate nucleus of the thalamus, the globus pallidus pars interna and, recently, the pallidothalamic tract; while research investigates the subthalamic nucleus, each target with distinct benefits and adverse event profiles. Early studies using magnetic resonance guided low intensity focused ultrasound show safe, transient blood brain barrier opening. First-in-human stem cells-derived dopaminergic grafts show safety and graft functioning. The advanced therapeutic landscape for Parkinson’s disease has evolved through innovations in established and novel therapies. Future priorities for the field include standardized biomarkers and protocols for adaptive deep brain stimulation, long-term evaluation of high intensity focused ultrasound outcomes, and rigorously controlled trials of low intensity focused ultrasound and cell-based therapies designed to assess disease-modifying potential.