iPS cell-based therapy for Parkinson's disease: A Kyoto trial

Area of Science:

• Stem cell research
• Neuroscience
• Regenerative medicine

Background:

• Induced pluripotent stem (iPS) cells offer potential for cell replacement therapy.
• Significant challenges, termed the "Valley of Death", hinder clinical translation of iPS cell research.
• Parkinson's disease is a key target for regenerative medicine approaches.

Purpose of the Study:

• To develop an efficient method for inducing dopaminergic neurons from human iPS cells.
• To identify and sort dopaminergic progenitor cells using the floor plate marker CORIN.
• To assess the safety and efficacy of iPS cell-derived dopaminergic neurons for Parkinson's disease treatment.

Main Methods:

• Efficient induction of dopaminergic neurons from human iPS cells.
• Sorting of dopaminergic progenitor cells using the CORIN marker.
• Grafting of CORIN+ cells into Parkinson's disease model rats and monkeys.
• Pre-clinical studies with a clinical-grade iPS cell line.
• Initiation of a clinical trial for Parkinson's disease patients.

Main Results:

• Grafted CORIN+ cells demonstrated good survival and functioned as midbrain dopaminergic neurons.
• The treatment showed minimal risk of tumor formation in animal models.
• Successful pre-clinical studies paved the way for a clinical trial.
• A clinical trial for Parkinson's disease patients commenced in August 2018.

Conclusions:

• The developed method enables efficient generation and sorting of functional dopaminergic neurons from iPS cells.
• iPS cell-based therapy shows promise for treating Parkinson's disease with a good safety profile.
• Overcoming the "Valley of Death" requires robust scientific rationale, thorough pre-clinical studies, and well-designed clinical trials.