Can you imagine a cell that normally lives in the brain, that is born to pump, and that pumps in a way that naturally bypasses the main barrier (the blood-brain barrier) to getting drugs into the brain? If such as cell existed and one could make it, we would potentially have a way to treat not just one disease, but many, many diseases of the brain and spinal cord. With invaluable support from CIRM, we believe that we have figured out how to derive just such a cell. The goal of this proposal is to provide proof-of-concept (POC) for using these cells – which we refer to as stem cell-derived choroid plexus epithelial cells, or dCPECs – to treat brain and spinal cord diseases. In this proposal, we take advantage of an existing CIRM-funded team to target a disease that is ideal, in many ways, for this POC testing – Hurler’s syndrome, a fatal childhood disease that is caused by the absence of a single protein, which results in a slow and progressive brain degeneration that cannot be effectively treated. By engineering dCPECs to pump the missing protein at very high levels, our mission is to provide POC not only for regular dCPECs, but also for engineered dCPEC “superpumps” to treat patients with Hurler’s syndrome and a wide range of other brain and spinal cord diseases.
Our proof-of-concept proposal for therapies using stem cell-derived choroid plexus epithelial cells (dCPECs) should benefit the State of California and its citizens in a number of ways. In the short term, this project will provide employment, education and training in stem cell research for a handful of California residents, and will support California-based companies that provide supplies for the stem cell and biomedical research communities. In the longer term, success in the proof-of-concept research would provide the rationale for other dCPEC-based transplant approaches, studies and applications by academics and stem cell companies, and drug screens to identify compounds that can regulate dCPECs and allow for combined cellular-pharmacologic approaches that bypass the blood-brain barrier, a major roadblock to the development of pharmaceuticals for treating the brain and spinal cord. Such outcomes would ultimately stimulate investment in California-based companies and benefit the health of many California citizens, which could ultimately reduce the economic burden of health care in the state.