California's Stem Cell Agency

Our goal is to provide autologous neuron replacement therapy for people with Parkinson's disease (PD) that will reverse the symptoms of their disease for several decades. PD is a progressive neurodegenerative disorder in which a specific cell type, dopamine neurons, are lost in a specific part of the brain, the substantia nigra. When the disease is diagnosed, more than half of these neurons are gone, causing movement disorders that worsen with time and are irreversible with conventional therapies. Neuron replacement therapy for PD was first tested in the 1980s, by groups in Sweden and the US that transplanted brain tissue from early aborted fetuses into the region of the brain that normally receives dopamine from the neurons in the substantia nigra. Remarkably, some recipients fully recovered from PD symptoms, and the transplanted neurons survived and thrived in their brains for the rest of their lives, 20 to 30 years. We are using a new non-fetal source of dopamine neurons, using technology developed 10 years ago that allows us to generate induced pluripotent stem cells (iPSCs) from any person. Like embryonic stem cells, iPSCs are capable of becoming every cell type in the body, and we have developed methods to efficiently produce the exact type of dopamine neuron that is lost in PD in a culture dish. Our CIRM grant supported the preclinical testing of these dopamine neurons as a cell type to use for clinical trials for transplantation in PD patients. There are 3 similar projects worldwide that plan to use dopamine neurons derived from embryonic stem cells or unmatched iPSCs. Our project is different because we plan to use autologous cells for transplantation. This means that, unlike the other projects, we may not need to use immunosuppression, which is expensive and can have serious side effects. Our plans over the next two years are to obtain FDA approval for our neuron replacement therapy, and to begin treatment of patients in a clinical trial.