PD is the second most common neurodegenerative disorder with an annual incidence of 60,000 and costs of $ 25 billion in the US alone. There is no current cure for PD. Pre-clinical research shows that at earlier pathological stages, brain neurons retain some characteristics to recover if they are in an optimal neural repair media. Our research investigates a new therapeutic approach to provide such media using autologous peripheral nerve grafts as a source of the neural repair cells.  We are running two clinical trials which feature the implantation of autologous sural nerve (SN) grafts targeted to the Substantia Nigra in combination with DBS for the treatment of PD patients.

Our research aims to investigate the therapeutic potentials of autologous peripheral nerve tissue grafting combined with Deep Brain Stimulation (DBS) to treat Parkinson's disease (PD).

The nerve grafts receive a conditioning injury pre-implantation to induce the repair phenotype. This phenotype was validated through RNA sequencing. So far, our clinical trial has involved 60 PD patients and the long-term effects are assessed using MDS-UPDRS III. To further study the neurobiology of the grafts, human SN tissue was also grafted in the striatum of athymic nude rats (Neuro-Avatar). The animals’ brains were processed and analyzed at 2 weeks and 6 months post-implantation.

The two-year follow-up data demonstrated a remarkable improvement in the motor scale of participants who received DBS plus a single unilateral graft in the Substantia Nigra. RNA seq of the grafts shows transcriptome changes consistent with the expected pro-regenerative changes of transdifferentiated repair Schwann cells and a significant downregulation of PD-related genes. Neuro-Avatar brains revealed a substantial graft cell survival plus remarkable neuronal changes in the surrounding brain tissue.

The regenerative changes in the peripheral nerve tissue may hold therapeutic potentials to treat neurodegenerative diseases like Parkinson’s disease.