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Abstract

Background and Objectives: Cholinergic degeneration in the nucleus basalis of Meynert (NBM) is implicated in the cognitive impairment seen in Parkinson disease (PD) and is being examined as a potential therapeutic target. We have previously shown the safety of delivering investigational autologous cell-based therapy, ie, peripheral nerve tissue (PNT), to the substantia nigra (SN) at the time of deep brain stimulation (DBS) surgery in PD (DBS-Plus). In this study, we assessed the safety and feasibility of simultaneously delivering that PNT to both the NBM and SN at the time of DBS.

Methods: Two patients with idiopathic PD and mild cognitive impairment, who underwent clinically indicated bilateral globus pallidus internus DBS, were consented for participation. At the time of lead placement, reparative autologous PNT (sural nerve) was harvested and stereotactically delivered to the NBM and SN contralateral to the patients' more severe motor symptoms.

Results: Delivery of PNT to both the SN and NBM was successfully achieved in both participants. There were no serious adverse events related to the delivery of the graft, and no adverse radiologic effects were observed. Both participants showed stable performance on standard PD testing. Neurocognitive testing at 18 months postoperatively in one participant showed expected decrements in certain domains and unique improvements in others.

Conclusion: We report the feasibility and preliminary safety data of stereotactic delivery of reparative autologous PNT to two separate unilateral targets at the time of DBS lead placement. We plan to continue exploring the potential for this investigational cell-based therapy to restore function to damaged networks in PD.

Document Type

Article

Publication Date

2026

Notes/Citation Information

© The Author(s) 2025. Published by Wolters Kluwer Health, Inc. on behalf of Congress of Neurological Surgeons. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Digital Object Identifier (DOI)

https://doi.org/10.1227/neuprac.0000000000000189

Funding Information

This work was supported by gifts to the UK Neurorestoration Center; Ann Hanley Neuroscience Fund; Pro’s Players FORE Parkinson’s; the National Center for Advancing Translational Sciences, through NIH grant UL1TR001998; and NIA 1R01AG081356.

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