“It was quite a wild idea,” said Lorenz Studer, Director of Memorial Sloan-Kettering Cancer Center’s Center for Stem Cell Biology and new MacArthur Foundation “genius” grant recipient. He’s talking about the obsession that’s shaped his life since he was a young medical student in Switzerland a quarter of a century ago: a question that just might change the way medicine works. Is it possible to create and transplant brain tissue to heal conditions like Parkinson’s disease?
“My target was always to use this for Parkinson’s,” he said. The disease, which affects about two of every 1,000 people, is found in those whose brains stop producing dopamine. This neurotransmitter is like the brain’s messenger — and when the brain isn’t able to send messages properly, things, such as motor skills and balance, start to break down.
When Studer learned about how Parkinson’s affects dopamine neurons, he started to wonder if transplantation could be a cure. The idea of transplanting working cells from fetal tissue was “quite radical at the time,” he recalls, but it made sense. “The more I started looking into it, the more clear it was that at least some fetal cells could survive in a brain and hook up with existing cells.” He began pushing for clinical trials using fetal tissue — and ran into an unexpected brick wall.
Not only were there ethical considerations about using material from aborted fetuses, but it turns out that fetal tissue isn’t a great source of working cells. “On the one hand it was very exciting,” said Studer. But on the other, it seemed clear that he just wouldn’t be able to generate the amount of viable material needed to actually treat the brain.
Enter the embryonic stem cell. Also called pluripotent stem cells, these cells have the potential to become anything and everything in the body — from hearts to bones to neurons. Studer is obsessed by the seemingly unlimited possibilities. “It’s like the bread that never stops feeding people in the Bible,” he said. “You can grow and grow and grow them. They can make millions and billions of cells. They could be anything.”
There’s just one problem: These tiny powerhouses have minds of their own. Pluripotent stem cells want to turn into embryos — and if left unchecked, they’ll transform into things like ears, guts and organs. Studer and his colleagues worked to figure out a way to coax them into a particular kind of cell. They achieved it by learning what he calls “the syntax of embryonic stem cells”: the particular cues that make the difference between a potential neural cell and an actual one. “It’s like a language or a piece of music,” said Studer. “Cells constantly have to make decisions. If you figure out how to push the fate of cells toward one decision or the other, you get exquisite access to a high number of cell types.”
Armed with a new language, the cell whisperer headed into clinical trials with a bunch of “beautiful” petri dishes and the conviction that the properly-signaled cells could be implanted into human subjects. It wasn't quite so simple: Though the process created working dopamine cells in mice, it just didn’t gel in humans. In fact, it would be eight years before Studer and his team figured out that dopamine neurons are actually an outlier in the land of cells, and would require more work.
“It’s a very specific cell type,” he said — and one well worth waiting for. After years of painstaking trials, Studer and his team have it down. Through their work with both embryonic and induced pluripotent stem cells, they’ve conducted extensive clinical trials in which they create and transplant reliable, working dopamine neurons in animals. If everything goes according to plan, he’ll test the method in human patients as early as 2017.
He thinks the trial will be a success. “If nature can do it, we can do it, too,” he insisted. If he succeeds, he hopes not just to unlock cures for people with neurodegenerative diseases, but better ways to model diseases for pharmaceutical companies and even individuals. And he hopes his team can start to focus on an intriguing detour suggested by their current work with stem cells: Learning more about how to move cells forward (and backward) in age.
For now, he plans to leverage his $635,000 in grant money to help secure even more ambitious investment in stem cell research and clinical trials. “Soon there will be a sea change in how the industry views stem cells,” he predicted. With the help of this newfound funding, Studer hopes to invest in younger colleagues who will further the field long after neural transplantation for conditions like Parkinson’s become routine. Oh, and he's also getting a new bike. An avid sportsman, Studer will replace his 15-year-old model with one that’s a bit more current. “You have to keep going on different levels other than just science,” he said, laughing. Just because some ideas are wild doesn’t mean they’re not inspired.