Objective: We report a patient with Parkinson’s disease (PD) who underwent deep brain stimulation (DBS) simultaneously with peripheral nerve graft in substantia nigra (SN) and the post-mortem analysis on integration of graft tissue.

Background: Currently, there are no medical or surgical therapies which have proven benefit to stop or slow the progression of PD. To alter disease progression, we propose cell-based graft that consists of peripheral nerve tissue as a source of growth factors and growth promoting proteins for delivery into the parenchymal region with dopaminergic cell loss (2). Clinical trial registration no: NCT01833364 (clinicaltrials.gov).

Method: A 73-year-old man with PD whose symptoms started at age 63 with right upper extremity shaking and slowness, was deemed to be DBS candidate for tremor predominance and significant fluctuations of symptoms. Levodopa equivalent dose (LED) was 600 before surgery. Neuropsychology evaluation did not reveal any cognitive impairment. He underwent DBS surgery along with peripheral nerve graft at the age of 70.

Results: Pre-surgical Dopamine active transporter (DAT) scan revealed decreased dopamine uptake bilaterally (left>right), while 2 years later (post-operative) showed worsening of findings bilaterally (right>left). Post-Surgery UPDRS Part III score at medication-off/stimulation-off phase showed improvement at 6,12,18 and 24 months compared to pre-operative UPDRS Part III score at medication-off phase. At 24 months we observed 9 point improvement from baseline in UPDRS Part III score. 24 month MRI was unremarkable. Participant was monitored for 34 months and no safety issues were observed related to graft delivery. After complications secondary to bowel obstruction and pneumonia, participant died. Brain autopsy was performed and it did not indicate any complications related to the procedure. The brain tissue showed Tyrosine hydroxylase positive staining ipsilateral to the graft in the SN.

Conclusion: These results support the idea that the peripheral nerve graft delivery might account for the improvement in UPDRS score and early histology results supports affects on the dopaminergic neurons proximal to the graft target. These results continue to support the further exploration of DBS plus as a safe, feasible option which could play a role in slowing the progression of PD.

References: 1. Bernheimer H, Birkmayer W, Hornykiewicz O, Jellinger K, Seitelberger F: Brain dopamine and the syndromes of Parkinson and Huntington. Clinical, morphological and neurochemical correlations. J Neurol Sci 20:415–455, 1973. 2. Van Horne CG, Jorge Quintero, Greg Gerhardt et al. Peripheral nerve grafts implanted into the substantia nigra in patients with Parkinson’s disease during deep brains cumulation surgery: 1-year followup study of safety, feasibility and clinical outcome. J Neurosurgery Feb 2018. 3. Perlow MJ, Freed WJ, Hoffer BJ, Seiger A, Olson L, Wyatt RJ. Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system. Science 1979;204: 643-647. 4. Björklund A, Stenevi U. Reconstruction of the nigrostriatal dopamine pathway by intracerebral nigral transplants. Brain Res 1979; 177: 555-560. 5. Olanow CW, Goetz CG, Kordower JH, Stoessl AJ, Sossi V, Brin MF, et al: A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson’s disease. Ann Neurol 54:403–414, 2003 6. Thompson V. Successful brain grafting. NY Med J 1890; 51: 701-702.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/evidence-of-survival-and-integration-of-implanted-autologous-peripheral-nerve-graft-in-substantia-nigra-in-a-patient-with-parkinsons-disease/