Abstract
OBJECTIVE Currently, there is no treatment that slows or halts the progression of Parkinson's disease. Delivery of various neurotrophic factors to restore dopaminergic function has become a focus of study in an effort to fill this unmet need for patients with Parkinson's disease. Schwann cells provide a readily available source of such factors. This study presents a 12-month evaluation of safety and feasibility, as well as the clinical response, of implanting autologous peripheral nerve grafts into the substantia nigra of patients with Parkinson's disease at the time of deep brain stimulation (DBS) surgery. METHODS Standard DBS surgery targeting the subthalamic nucleus was performed in 8 study participants. After DBS lead implantation, a section of the sural nerve containing Schwann cells was harvested and unilaterally grafted to the substantia nigra. Adverse events were continually monitored. Baseline clinical data were obtained during standard preoperative evaluations. Clinical outcome data were obtained with postoperative clinical evaluations, neuropsychological testing, and MRI at 1 year after surgery. RESULTS All 8 participants were implanted with DBS systems and grafts. Adverse event profiles were comparable to those of standard DBS surgery with the exception of 1 superficial infection at the sural nerve harvest site. Three participants also reported numbness in the distribution of the sural nerve distal to the harvest site. Motor scores on Unified Parkinson's Disease Rating Scale (UPDRS) part III while the participant was off therapy at 12 months improved from baseline (mean ± SD 25.1 ± 15.9 points at 12 months vs 32.5 ± 9.7 points at baseline). An analysis of the lateralized UPDRS scores also showed a greater overall reduction in scores on the side contralateral to the graft. CONCLUSIONS Peripheral nerve graft delivery to the substantia nigra at the time of DBS surgery is feasible and safe based on the results of this initial pilot study. Clinical outcome data from this phase I trial suggests that grafting may have some clinical benefit and certainly warrants further study to determine if this is an efficacious and neurorestorative therapy.
Original language | English |
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Pages (from-to) | 1550-1561 |
Number of pages | 12 |
Journal | Journal of Neurosurgery |
Volume | 129 |
Issue number | 6 |
DOIs | |
State | Published - 2018 |
Bibliographical note
Funding Information:We thank Ann Hanley for her help and support with the study participants. Funding was provided by the National Center for Advancing Translational Sciences through National Institutes of Health grant UL1TR000117. The content is solely the responsibility of the authors and does not necessarily represent the official views of National Institutes of Health.
Funding Information:
This work was supported by gifts from the Brain Restoration Center, Tom Dupree for Parkinson’s Disease Research, and Pro’s Players Fore Parkinson’s. Dr. Gerhardt: previously received research support from Medtronic. Dr. Slevin: received educational support grants from Medtronic. Dr. van Horne: received educational support grants from Medtronic.
Publisher Copyright:
© AANS 2018 except where prohibited by US copyright law
Keywords
- Cell therapy
- Deep brain stimulation
- Functional neurosurgery
- Multimodal DBS
- Neurotrophic factor
ASJC Scopus subject areas
- Surgery
- Clinical Neurology