HSCI Retreat 2019 Abstract 3

ABSTRACT

Parkinson’s disease (PD) is a progressive degenerative disease. Patients present with motor symptoms characterized by tremor, bradykinesia, rigidity and postural instability. There are approximately 1.5 million diagnosed cases in the United States. At the time of diagnosis about 60% of the midbrain dopamine (mDA) neurons have already degenerated. Cell replacement therapy using cell preparations from fetal ventral midbrain has shown promise in clinical studies. Some of the drawbacks with this approach are that it is not scalable for a large patient population and require immunosuppression. Therefore, our goal is to develop an autologous approach using iPSCs generated from affected PD patients’ blood cells and differentiate them into transplantable mDA cells. The mDA cell preparations will be cryopreserved for quality control testing and use in patient autologous transplantations. We have previously shown proof-of-principle of autologous transplantations in non-human primates (NHPs) [Hallett et al., 2015, Cell Stem Cell, 16(3), 269-274] and have now performed additional proof-of-principle and safety studies in NHPs that demonstrate the safety and efficacy of this approach (Figure 1). Additionally, we have in preparation for IND-enabling studies obtained critical data on human mDA cell preparations, including in vitro cell content, post-thaw stability, cell preparation dosing reproducibility and in vivo survival and functionality of cryopreserved mDA cells in rodents.