Astrocytes to the Rescue in Parkinson's
By transforming other nearby brain cells, researchers restore lost dopamine neurons in mice bred to develop Parkinson's Disease.
Researchers investigating Parkinson’s disease can attest to the disease’s stubborn resistance to treatment. There was a burst of optimism a few years ago when it appeared that stem cell therapy might offer a cure, but hope was clouded when the stem cells turned out to produce unwanted behavioral side effects.
Parkinson’s results from a loss of “functional dopamine neurons” in a part of the brain called the substantia nigra. These neurons make filaments called axons, some of which communicate with the basal ganglia, the brain tissue that manages motor control. Thus, when the dopamine neurons in the substantia nigra die off, the patient develops tremors. Eventually she will also have dementia as the disease affects other parts of the brain.
Now, another potential game-changer has been reported in a study published in Nature Biotechnology on April 10. Instead of converting a stem cell to a dopamine neuron in a test tube and then transporting it into a Parkinson’s victim’s brain, a team led by Ernest Arenas at the Karolinska Institute in Stockholm isolated the transcription factors that comprise those conversion instructions.
The researchers were able to convert human astrocytes into functional human dopamine neurons in a test tube.
They used a virus to carry the transcription factors into the nuclei of astrocytes, a common and abundant type of brain cell that was already present in the brains of mice bred to develop Parkinson’s. Transporting transcription factors by virus is much easier than transporting whole live cells into a brain, said Marius Wernig, a pathologist at Stanford University in California and a study co-author.
The injected transcription factors successfully converted the mice’s astrocytes into neurons that could make dopamine, and the mice’s symptoms lessened dramatically. In a separate experiment, the researchers were also able to convert human astrocytes into functional human dopamine neurons in a test tube; they have not tried it in human Parkinson’s sufferers, however.
“Being able to reprogram any cells to make another cell type and to do it in a living animal is pretty spectacular,” said Joseph Quinn, Director of the Oregon Health and Science University Parkinson Center and Movement Disorder Program in Portland. Quinn was not involved in the study.
“They had some data to show that it was functionally relevant -- that the animals’ gait was improved,” he adds, emphasizing that the technique could have real-world benefits.
However, before Parkinson’s patients rush to receive this treatment, both Wernig and Quinn urge caution. It’s still a long way from FDA approval. Many therapies, including some stem cell conversion processes, have been tried and discarded. Some have worked well in animals but failed to work in humans.
Any method that encourages cells to grow, said Quinn, is risky. “When you’re manipulating cell growth, could you cause some cells to grow out of control? That’s a cancer, right?” Quinn said.
Being able to reprogram any cells to make another cell type and to do it in a living animal
In the current study, the researchers did not observe any tumors in the mice.
However, Wernig also cites earlier studies of other treatments in which some patients experienced improved symptoms at first, only to have their brain cells later “overreact” and cause more severe movement problems called dyskinesia. And if the treatment involves inserting or converting cells in the brain, he adds, there’s no way to stop or withdraw the treatment if something goes wrong.
Thus, Wernig said, the current study is “a big step forward — but a big step in the very beginning.”