Objective: Evaluate the safety and feasibility of unilateral cell-based therapy delivery to the putamen and substantia nigra in patients with Parkinson’s disease (PD) undergoing deep brain stimulation (DBS) surgery.

Background: We have previously trialed the use of “repair” Schwann cells (Schwann cells transdifferentiated after injury) exclusively targeted to the substantia nigra to alter the progression of PD. However, dopaminergic terminals in the putamen are also affected in PD and are a key target for intervention.

Method: Three participants (2 female, 1 male, age 56, 60, and 61 years old) with an existing unilateral DBS lead to the subthalamic nucleus were deemed candidates for DBS lead placement to the side contralateral to the existing lead. After undergoing DBS lead placement to the globus pallidus internus (GPi),  autologous peripheral nerve grafts (activated sural nerve – previously injured through transection during Stage I of a standard two stage DBS surgery) were implanted unilaterally into 3 separate sites in the putamen and one site in the substantia nigra.  Participants are followed for 12 months after surgery with study visits at 6 months and 12 months.

Results: Mean OFF medication scores at baseline on the MDS-UPDRS Part III were 53 ± 5 points and ON scores were 24.7 ± 11.5 points. All three participants successfully received a DBS lead to the GPi. In addition, all participants received 3 graft deployments to the putamen and 1 deployment to the substantia nigra on the side ipsilateral to the GPi DBS lead. Adverse event profile was comparable to standard DBS surgery. MRI scans were unremarkable in the perioperative period. At six months, one participant showed a 10 point improvement OFF medication/OFF stimulation; however, unlike our previous studies, the 2 other participants failed to attend the 6 month study visit, in part, because of difficulty with traveling out-of-state. An incidence rate of 66% missed follow-up visit is well over our standard rate and negatively affects our study feasibility metrics.

Conclusion: Unilateral grafts of autologous peripheral nerve to the putamen and substantia nigra at the time of DBS surgery indicate a safe profile, but follow-up visit complications may suggest a need for modifying study design.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/unilateral-delivery-of-cell-based-therapy-to-the-putamen-and-substantia-nigra-in-patients-with-parkinsons-disease-who-have-an-existing-dbs-system/