Merging DBS with viral vector or stem cell implantation: "hybrid" stereotactic surgery as an evolution in the surgical treatment of Parkinson's disease

Abstract

Parkinson's disease (PD) is a complex neurodegenerative disorder that is currently managed using a broad array of symptom-based strategies. However, targeting its molecular origins represents the potential to discover disease-modifying therapies. Deep brain stimulation (DBS), a highly successful treatment modality for PD symptoms, addresses errant electrophysiological signaling pathways in the basal ganglia. In contrast, ongoing clinical trials testing gene and cell replacement therapies propose to protect or restore neuronal-based physiologic dopamine transmission in the striatum. Given promising new platforms to enhance target localization-such as interventional MRI-guided stereotaxy-the opportunity now exists to create hybrid therapies that combine DBS with gene therapy and/or cell implantation. In this mini-review, we discuss approaches used for central nervous system biologic delivery in PD patients in previous trials and propose a new set of strategies based on novel molecular targets. A multifaceted approach, if successful, may not only contribute to our understanding of PD pathology but could introduce a new era of disease modification.