Introduction: No treatment halts or modifies the course of clinical decline of motor and non-motor symptoms in Parkinson's disease (PD). Cognitive impairment is one of the most troubling non-motor symptoms and is associated with a loss of cholinergic neurons in the nucleus baslalis of Meynert (NBM). Nerve growth factor (NGF) has been shown to support the cell maintenance and survival of cholinergic neurons in experimental models. We tested the safety and feasibility of transplanting autologous peripheral nerve grafts (APNGs), containing Schwann cells which have been shown to produce NGF, into the NBM in PD patients with mild cognitive impairment (NCT02369003). Grafts were placed at the time of bilateral deep brain stimulation (DBS).
Methods: Five subjects have participated currently. All had a diagnosis of idiopathic PD with MCI, demonstrated from a comprehensive pre-operative neurocognitive exam. Subjects were good candidates for bilateral DBS of the globus pallidus internus. APNGs were harvested from the sural nerve and deposited unilaterally into the NBM, targeted electrophysiologically, contralateral to the most symptomatic side. Subjects were followed clinically for adverse events. Post-op MRIs were obtained within 24 hours.
Results: Subjects were successfully implanted with APNGs to the NBM. MRIs demonstrated safe graft implantations without hemorrhage or edema. There were no significant adverse effects related to graft implantation within the perioperative period. One subject has been evaluated postoperatively at 3 months and 8 months with follow-up neurocognitive evaluations showing stable diminished scores in verbal fluency tests (also observed in DBS patients) and substantial improvements in semantic fluency and psychomotor speed.
Conclusions: Evidence is provided that our DBS Plus approach is safe and feasible. This is in agreement with our previous studies of APGNs implanted into the substantia nigra (n=19). Results are preliminary. Full evaluations will be performed through 24 months.
Patient Care: There is currently no treatment that halts or modifies the progressive motor or non-motor symptoms of PD. This research is aimed at developing a restorative, cellular therapy targeting cognitive impairments found in patients with PD. If successful, autologous peripheral nerve grafts could provide a therapeutic strategy to alter the continued clinical decline observed in PD patients with MCI
Learning Objectives: The targeted audience should be able to: 1) Understand the rationale for using peripheral nerve tissue as a source of grafting material to support host cell survival, 2) Understand the benefits of DBS Plus as a platform for investigating therapies requiring surgical access to brain targets, including cell based therapies, gene therapies, and delivery of growth factors, 3) Understand the stereotactic targeting of the NBM