Introduction: Currently two clinical trials (NCT01833364 and NCT02369003) are underway which feature the implantation of a peripheral nerve autograft to the brain (targeted to the Substantia Nigra) in combination with Deep Brain Stimulation (DBS) for the treatment of patients with Parkinson’s disease. As of 1/8/2018, 46 patients have received a graft. This nerve tissue is harvested from the sural nerve, a cutaneous sensory nerve located in the lateral ankle, from patients undergoing DBS surgery. The tissue receives a conditioning injury in situ two weeks prior to grafting.
This study aims to characterize the effect of this conditioning, as well as the state of the nerve graft tissue immediately prior to implantation.
Methods: Two sural nerve tissue samples (pre-conditioned and post-conditioned) per patient were collected from six patients during DBS surgeries 14 days apart. RNA sequencing (RNA-seq) was used to measure absolute and relative levels of gene transcripts in the pre-conditioned and post-conditioned nerve tissue. These findings were supplemented by histology of the nerve tissue.
Results: The results of these experiments show: 1) Consistent similarity within the pre-conditioned and post-conditioned group transcriptomes 2) Consistent changes between the pre-conditioned and post-conditioned group transcriptomes 3) Increased transcript levels related to nerve repair, growth factor production, and immune cell migration pathways 4) Decreased transcript levels related to myelin production pathways, consistent with the repair Schwann cell phenotype. All results are statistically significant (p < 0.05).
Conclusions: These findings suggest that the nerve graft tissue implanted in human patients has a pro-regenerative phenotype which has the potential to alter the course of neurodegeneration in the brain.
Patient Care: This research answers basic science questions about nerve graft tissue that were generated by an ongoing clinical trial. These results will directly inform future clinical decisions regarding protocol optimization and multi-site implementation.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe how peripheral nerve grafts are being used in DBS surgeries for the treatment of Parkinson’s disease 2) Describe the effect of a conditioning injury on the peripheral nerve