Direct delivery of an investigational cell therapy in patients with Parkinson's disease: an interim analysis of feasibility and safety of an open-label study using DBS-Plus clinical trial design

BMJ Neurol Open. 2022 Jul 14;4(2):e000301. doi: 10.1136/bmjno-2022-000301. eCollection 2022.

Abstract

Objective: To evaluate the interim feasibility, safety and clinical measures data of direct delivery of regenerating peripheral nerve tissue (PNT) to the substantia nigra (SN) in participants with Parkinson's disease (PD).

Methods: Eighteen (13 men/5 women) participants were unilaterally implanted with PNT to the SN, contralateral to the most affected side during the same surgery they were receiving deep brain stimulation (DBS) surgery. Autologous PNT was collected from the sural nerve. Participants were followed for safety and clinical outcomes for 2 years (including off-state Unified Parkinson's Disease Rating Scale (UPDRS) Part III assessments) with study visits every 6 months.

Results: All 18 participants scheduled to receive PNT implantation received targeted delivery to the SN in addition to their DBS. All subjects were discharged the following day except for two: post-op day 2; post-op day 3. The most common study-related adverse events were hypoaesthesia and hyperaesthesias to the lateral aspect of the foot and ankle of the biopsied nerve (6 of 18 participants experienced). Clinical measures did not identify any hastening of PD measures providing evidence of safety and tolerability. Off-state UPDRS Part III mean difference scores were reduced at 12 months compared with baseline (difference=-8.1, 95% CI -2.4 to -13.9 points, p=0.005). No complications involving dyskinesias were observed.

Conclusions: Targeting the SN for direct delivery of PNT was feasible with no serious adverse events related to the study intervention. Interim clinical outcomes show promising results meriting continued examination of this investigational approach.

Trial registration number: NCT02369003.

Keywords: NEUROSURGERY; PARKINSON'S DISEASE; SCHWANN CELL.

Associated data

  • ClinicalTrials.gov/NCT02369003