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School of Medicine
Dr. Ted Dawson,
professor of neurology
and co-director of the
Program, a division
of the Institute for Cell
Engineering at Johns
We’re creating induced pluripotent stem (iPS) cells from patients with Parkinson’s disease with the intent of turning them into dopamine neurons that we can study in a dish and also put into animals. We want to see if human iPS derived neurons grown in culture or in a mouse can lead to disease, and if it can, to study the mechanisms of why cells degenerate and test our hypotheses, drugs and targets in human cells.
If you look at the work that’s been done in neurodegenerative diseases in animal models, we’ve been good at slowing progression of disease, but when we go to humans, the trials fail. So why is that? Perhaps because in mice we’re able to intervene very early in the disease, but in humans we’re treating late. Maybe the treatment would work if we treated early in humans, but this would require the ability to diagnosis the disease prior to the onset of symptoms. The other possibility is that Parkinson’s disease in a mouse is different than a man.
Human stem cell.
Using iPS cells we can test new therapies in human neurons for the first time. One of the reasons there have been tremendous new therapies with cancers is that scientists can biopsy human tumors and use those cells to design drugs. Now stem cells are putting us in a position to be able to study neurodegenerative diseases in a similar way.
For developmental diseases such as Down syndrome and schizophrenia, there’s no question in my mind that iPS will change the ways those diseases are studied and treated. With an adult-onset neurodegenerative disorder that takes 50 years to develop in humans, the big question is whether an iPS cell will have Parkinson’s disease after growing in a mouse for a few months. We just don’t know. But we need to do the experiment.
Lots of people thought Parkinson’s was going to be low hanging fruit for stem cell transplantation. But we still don’t fully understand the transplantation process and how to optimize it. There needs to be a lot of work done to get to that point. And medical therapy for Parkinson’s is so advanced that transplantation right now probably isn’t going to be any better than what we can already do. But that doesn’t mean we shouldn’t be forging ahead, using stem cells to discover more about the disease in order to find new drugs as well as refine our ideas about transplantation.
--Interviewed by Maryalice Yakutchik