Stem cell science meets public health: Case study, Parkinson’s disease

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Geoff Lomax is CIRM’s Senior Officer to the Standards Working Group 
As a student of public health, I have always been a believer in public science. Public science is critical for providing sustained capacity for research. As othershave pointed out, this capacity translates into important commercial potential. Historically, California has been a leader in investing in public science. From its network of universities and various health-oriented agencies, the state maintains a wealth of information, technical and human resources. Capacity such as this lays the groundwork for innovation as researchers from varying disciplines interact to imagine new ways forward.
One personally exciting conversation that has emerged in the past couple of years is the role of stem cell science in supporting our understanding of environmental influences on health and disease. In fact, the National Institutes for Environmental Health Sciences has begun to fund research addressing the potential of environmental exposures to alter function, proliferation, survival, and differentiation of stem cells (here is a link to that RFA). One area of particular interest is the development of cellular systems to model the disease process. As we reported in a report on a toxicology meeting, these model systems help us both understand disease and evaluate therapies.
At CIRM, we thought it would be informative to hear from one of our grantee institutions that has been exploring this space. At a recent seminar, researchers from The Parkinson’s Institute reported on their work studying the relationship between environmental influences and development of Parkinson’s disease. A novel studyin twins conducted by Samuel Goldman MD, MPH and Caroline M. Tanner, MD, PhD, from The Parkinson’s Institute has found that exposure to trichloroethylene (TCE) – a hazardous contaminant now found in soil, groundwater and air – can raise a person’s risk of developing Parkinson’s disease by six times. That’s just one of several contaminants and pesticides that increase risk of the disease.
The Parkinson’s Institute has taken skin samples from patients with the disease and reprogrammed those into an embryonic-like state. So far, they’ve developed 45 of these so-called induced pluripotent stem cell lines (iPSCs). (Some of this work was done with a CIRM Early Translational Award.) In the process of developing these lines, researchers collected information relating to environmental factors (job and residential history, lifestyle and others) associated with health and disease. Dr. Birgitt Schuele discussed ways in which these cells could be applied in future public health research.
One intriguing line of inquiry related to examining how pesticide exposure may be associated with Parkinson’s disease risk. Goldman and Tanner reported on how certain pesticides cause Parkinson’s disease in animal models and exposure is also associated with disease in humans. Schuele suggested patient iPSCs are a valuable tool for further studying this association and the disease process. The idea is that the researchers can mature those cells into the cell type that is associated with the disease—called dopaminergic neurons. Then they can expose those neurons to the pesticide to see if the neurons show signs of the disease in a lab dish. This is a critical way of learning about the effects of compounds on human cell types.
This type of research represents a way to leverage existing investments in California’s unique information, technical and human resources. For example, the state’s pesticide use reporting and visionary investment in mapping tools offers a unique opportunity to connect basic research on disease with information relating to the distribution of environmental agents. Thanks to a bill supported by then-Senator Art Torres (now CIRM vice chair) California has the most comprehensive data on pesticide use of any state. These resources have been used previously to study other disease such as autism. Videos from a seminar on the relationship between pesticide use and autism are available on CIRM’s YouTube channel.
The application of stem cell tools from basic research towards public health and environmental protections represents a critical avenue for health promotion and disease prevention. It’s personally exciting to see CIRM grantees making use of public resources to carry out science with such a potential for public good, and to have the NIEHS recognizing the value of this research with their funding initiative.   
G.L.

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