Study Rationale:
Cell replacement using induced pluripotent stem cells (iPSCs) is a potential restorative therapy for Parkinson's disease. Replacing brain cells that produce dopamine, a chemical affected in Parkinson's, could address both motor symptoms, as well as L-dopa-induced dyskinesias. The team, with previous MJFF funding, has completed pre-clinical dose-escalation studies demonstrating long-term survival and safety of transplants using a person's own cells (i.e., autologous). They were able to develop a protocol for creating midbrain dopamine cells from human iPSCs. In previous studies, dopamine-producing stem cells grafts provide physiologically appropriate dopamine release in the brain. Such cell replacements may be more effective in treating the motor symptoms of Parkinson's long-term than current therapies.
Hypothesis:
Replacing midbrain dopamine (DA) neurons in PD is a rational treatment to reduce or prevent the motor symptoms of PD, and L-dopa-induced dyskinesias. This treatment provides a scalable autologous cell replacement therapy for PD.
Study Design:
In this project, we will optimize the freezing and transplantation protocol for dopamine brain cell survival. Using iPSCs derived with the same method and in the facility that we plan to use for clinical applications, we will differentiate the iPSCs into midbrain dopamine cells and xeno-graft into pre-clinical models to determine long-term graft survival and functional improvement.
Impact on Diagnosis/Treatment of Parkinson's disease:
Replacing midbrain dopamine brain cells is a rational treatment to reduce or prevent the motor symptoms of Parkinson's and L-dopa-induced dyskinesias. It could provide a scalable cell replacement therapy for the disease.
Next Steps for Development:
The goal of this project is to obtain data to guide human clinical studies. Our next step would be to perform a pre-IND study and continue progress toward the clinic.