Past, present, and future of cell replacement therapy of Parkinson’s disease

Abstract

Given that the primary motor dysfunction in Parkinson’s disease (PD) results from the selective degeneration of midbrain dopamine neurons, cell replacement therapy represents a promising therapeutic approach. This potential has been demonstrated in multiple studies using human fetal mesencephalic cell transplantation. To address the limitations associated with fetal cell sources, we are developing and optimizing human iPSC-based transplantation for autologous, personalized cell therapy. Recently, we achieved a significant milestone by treating the first PD patient using the patient’s own iPSCs-derived dopamine neurons. However, this clinical study has also highlighted new challenges that require attention. Notably, we observed that the surgical procedure, termed "needle trauma," induces acute and severe innate immune responses that disproportionately affect grafted dopamine neurons.

In this presentation, I will discuss our current progress in cell replacement therapy and our ongoing Phase I/II clinical trial for PD patients, and complementary neuroprotective drug strategies aimed at maximizing therapeutic outcomes for patients.