Feasibility and Safety of autoloGous UncondItioneD pEripheral Nerve Tissue Delivery to the Substantia Nigra (GUIDE)

Feasibility and Safety of autoloGous UncondItioneD pEripheral Nerve Tissue Delivery to the Substantia Nigra

This is an open-label, non-randomized, single-arm trial design to actively follow participants for 12 months. Ten participants will be enrolled to receive bilateral delivery of Peripheral Nerve Tissue (PNT) to the Substantia Nigra at the time of Deep Brain Stimulation (DBS) surgery. After 12 months, participants will be followed long term through annual visits for the rest of their lives. Participants will serve as their own donor for the tissue.

We recently designed open-label safety studies to investigate the use of an autologous source of cellular tissue from the peripheral nervous system (van Horne et al., 2017, 2018; Quintero et al. 2022), reparative peripheral (sural) nerve tissue containing a variety of cells and neuroprotective factors (Chau et al. 2022). While our previous studies have used injury-activated peripheral nerve tissue (PNT), where the sural nerve is transected and allowed to regenerate in situ for up to about 2 weeks before implantation, here we propose to use naïve, previously uninjured, nerve tissue delivered bilaterally to the substantia nigra at the time participants are undergoing deep brain stimulation (DBS) surgery. Participants will be assessed preoperatively, then undergo DBS surgery and delivery of autologous PNT, and then assessed postoperatively at two weeks after surgery, 6 months, 12 months and annually thereafter for adverse events and clinical outcomes.

Inclusion Criteria:

• Undergoing DBS
• Diagnosis of clinically established or clinically probably PD (Parkinson's disease) as defined by MDS criteria
• Age 40-75, inclusive
• Able and willing to undergo ioflupane/SPECT
• Able to tolerate the surgical procedure
• Able to undergo all planned assessments
• Available access to the sural nerve

Exclusion Criteria:

• Any condition that would not make the subject a candidate for DBS
• Previous PD surgery or intracranial surgery
• Typical, nonparkinsonian syndrome ioflupane/SPECT signal
• Female who is pregnant, lactating, or of child-bearing potential unwilling to use an adequate birth control method during the period of the study
• Unable to undergo an MRI
• An obstructed trajectory path to the substantia nigra