Objective: Investigate safety, feasibility, and potential efficacy of cell therapy combined with DBS to treat and modify symptoms and progression of PD.

Background: Our strategy couples a biological therapy with DBS surgery in an attempt to restore areas of the brain affected in PD. Our cellular source consists of sural nerve autografts which contain Schwann cells, known to produce a host of growth factors demonstrating regenerative potential.

Methods: Standard stereotactic DBS surgery targeting STN or GPi. Section of sural nerve was excised, stripped of epineurium, cut into 1mm pieces, and unilaterally delivered into substantia nigra (SN) and/or nucleus basalis of Meynert (NBM). Adverse events continuously monitored. Assessments included neurocognitive performance, quality of life, gait, (123I-ioflupane) SPECT imaging, and MR imaging at baseline and at 24 months after implant surgery. Subjects undergo a UPDRS evaluation before surgery and at 6, 12, 18 and 24 months after surgery.

Results: We completed a 1-year Phase I study (NCT01833364) with STN DBS and a nigral graft and found adverse event profile comparable to standard DBS surgery. 6 of 8 participants showed a lower UPDRS III motor score than at baseline (25.5 ± 16.8 at 12 months vs. 32.5 ± 9.8 at baseline; Mean ± SD, N=8) considered a moderate clinically important difference (Shulman et al. 2010). Follow-up, open-label, two-year study of safety and feasibility (NCT02369003) has been initiated that allows GPi DBS and nigral or NBM graft placement. Mean age for participants was 65.0 ± 7.6 years (N=25), Hoehn & Yahr score: 3.0 ± 0.7, UPDRS III OFF medication: 37.8 ± 10.6, and UPDRS III ON medication: 18.9 ± 8.6. For participants who have reached 1-year time point and received graft to SN, motor scores were 28.0 ± 9.3 points vs. 35.0 ± 12.2 points at baseline (N=8). Collection for the other participants is ongoing. In total, we have successfully completed graft delivery to SN (N=26), to NBM (N=7), and to SN and NBM (N=1). Immediate post-operative MRIs showed no evidence of abnormal tissue disruption. There have been no serious adverse events related to graft placement.

Conclusions: Initial results from two clinical trials indicate a potentially safe and feasible means of delivering cell or biologic therapy with DBS and provide preliminary clinical evidence of baseline improvements at one year.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dbs-plus-investigating-cell-therapy-and-deep-brain-stimulation-as-an-approach-to-alter-disease-progression-and-treat-motor-and-non-motor-symptoms-of-parkinsons-disease/