Parkinson's disease (PD) is a devastating movement disorder caused by the death of dopaminergic neurons (a type of nerve cells in the central nervous system) present in the midbrain. These neurons secrete dopamine (a signaling molecule) and are a critical component of the motor circuit that ensures movements are smooth and coordinated.
All current treatments attempt to overcome the loss of these neurons by either replacing the lost dopamine, or modulating other parts of the circuit to balance this loss or attempting to halt or delay the loss of dopaminergic neurons. Cell replacement therapy (that is, transplantation of dopaminergic neurons into the brain to replace lost cells and restore function) as proposed in this application attempts to use cells as small pumps of dopamine that will be secreted locally and in a regulated way, and will therefore avoid the complications of other modes of treatment. Indeed, cell therapy using tissue-derived cells have been shown to be successful in multiple transplant studies. Work in the field has been limited however, partially due to the limited availability of cells for transplantation.
We believe that human embryonic stem cells (hESCs) may offer a potentially unlimited source of the right kind of cell required for cell replacement therapy. Work in our laboratories and in others has allowed us to develop a process of directing hESC differentiation into dopaminergic neurons. Parallel efforts by clinicians have identified processes to implant the cells safely and to follow their behavior in humans in a safe non-invasive fashion. Equally important, useful animal models for testing cell therapy have been developed. We therefore believe that the time is right to mount a coordinated team effort such as the one we have proposed to approval from the FDA to treat PD using dopaminergic neurons obtained from hESCs.
For this proposal we have built a California team with both scientists and clinicians that have the potential to translate a promising idea (a cell therapy for PD) to an IND submission. Our goals include: 1) Identifying a clinically compliant hESC line capable of differentiating into midbrain dopaminergic neurons; 2) Developing protocols for generating and purifying dopaminergic neurons on a large scale; 3) Transferring the protocols to a Good Manufacture Practice (GMP) facility and making clinical grade lots; 4) Testing the quality of the cells in suitable PD animal models (rodents and large animal models); 5) Collecting the data to submit to the FDA for permission to conduct a clinical trial.
This application to treat a currently non-curable disease (PD) meets CIRM's primary goal for Disease Team Research Awards and we believe our efforts will help take cell-based therapy for PD to the clinic.
Parkinson’s disease affects more than a million patients United States with a large fraction being present in California. California, which is the home of the Parkinson’s Institute and several Parkinson’s related foundations and patient advocacy groups, has been at the forefront of this research and a large number of California based scientists supported by these foundations and CIRM have contributed to significant breakthroughs in this field.
We have assembled a California based team of scientists and clinicians that aim to develop a cell replacement therapy for this currently non-curable disorder. We believe that this proposal which will hire more than thirty employees in California includes the basic elements that are required for the translation of basic research to clinical research. We believe these experiments not only provide a blueprint for moving Parkinson’s disease towards the clinic for people suffering with the disorder but also a generalized blueprint for the development of stem cell therapy for multiple neurological disorders including motor neuron diseases and spinal cord injury. The tools and reagents that we develop will be made widely available to Californian researchers and we will select California-based companies for commercialization of such therapies. We hope that California-based physicians will be at the forefront of developing this promising avenue of research. We expect that the money expended on this research will benefit the Californian research community and the tools and reagents we develop will help accelerate the research of our colleagues in both California and worldwide.