Autologous suraL nervE Grafting to the Substantia nigrA in Patients With Synuclienopathies

A Phase I Study of the Feasibility and Safety of SuraL nervE Tissue Grafting to the Substantia nigrA in Patients With Synucleinopathies (LEAP)

This phase I double-blind study focuses on the safety and feasibility of implanting autologous peripheral nerve tissue (PNT) into the substantia nigra area of the brain in persons who have been diagnosed with either Parkinson's disease (PD) or Multiple System Atrophy (MSA). 7 participants will be enrolled, with 4 participants receiving the graft and 3 receiving a sham surgery. Eligible participants will be early in their diagnosis with a lower burden of symptoms. Participants will be followed initially for one year after surgery.

This phase I double blind clinical trial will be used to plan future, larger clinical trials that would test how autologous cells from the peripheral nerve may help in the repair of damaged brain cells in Parkinson's Disease (PD) or Multiple System Atrophy (MSA) and slow the progression of the diseases. We will be judging the feasibility of implanting a participant's own cells from a nerve in the leg into the substantia nigra area of the brain. Patients eligible for participation will be at an earlier in stage of the disease with symptoms being less severe and therefore would not yet qualify for DBS. The LEAP trial is a study where the first participant will receive an implantation of the cells from their own sural nerve (a nerve near the ankle), into the substantia nigra on both sides of their brain. The 6 participants who follow, will be randomized to one of two arms. The 3 participants assigned to the experimental arm will receive the graft. The 3 participants assigned to the control arm will receive a sham surgical procedure, where the sural nerve will be biopsied, and bilateral scalp incisions will be made. Those who do not receive the cells initially may be eligible to undergo another surgery at the end of the study, after un-blinding has occurred, to receive the cell implants.

Inclusion Criteria:

• Diagnosis of clinically established or clinically probable PD or MSA as defined by MDS criteria
• Disease duration greater than 2 years
• Age 40-75, inclusive
• MDS-Unified Parkinson's Disease Rating Scale (UPDRS) Part III greater than or equal to 20 points but less than or equal to 35 points, off anti-parkinsonian medication for PD or MDS-Unified Multiple System Atrophy Rating Scale (UMSARS) less than or equal to 30 points off anti-parkinsonian medication
• No MDS-UPDRS Part III score >3 on items 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.14 while off medication
• 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:

• Previous PD surgery or intracranial surgery
• Ongoing major medical or psychiatric disorder incl. depression and psychosis
• Other concomitant treatment with neuroleptics
• Typical, nonparkinsonian syndrome ioflupane/SPECT signal
• Unable to undergo an MRI
• An obstructed trajectory path to the substantia nigra
• Significant microvascular disease
• Use of anticoagulants other than aspirin
• Female who is pregnant, lactating, or of child-bearing potential unwilling to use an adequate birth control method during the period of the study
• Consent capacity will be assessed and determined during and throughout a participant's neuropsychological exam. A participant who experiences a decline in consent capacity prior to surgery, will be removed from the study by the PI. A decline in consent capacity after surgery will not result in the removal of the participant in the study.