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Monday, April 10, 2017

Brain cells reprogrammed to make dopamine, with goal of Parkinson’s therapy

April 10, 2017

In a pioneering study, European scientists have “reprogrammed” brain cells in mice to correct some of the movement disorders of Parkinson’s disease.
The scientists also demonstrated the reprogramming in human brain cells grown in cultures.
In both mice and human cell cultures, the procedure converted brain cells called astrocytes into cells that produce dopamine, a neurotransmitter necessary for movement. Dopamine-making neurons are destroyed in Parkinson’s disease; so replacing them should alleviate symptoms.
Like all biomedical research, this approach will require more development and testing before it can be considered for treating actual patients.
The study was published Monday in Nature Biotechnology. Pia Rivetti di Val Cervo was first author, and Ernest Arenas was senior author. Both are of Karolinska Institute in Stockholm, Sweden.
The study can be found online at
Researchers worked on mice that had had their dopamine-making neurons destroyed. They used a viral delivery system to transmit three genes to the astrocytes that reprogrammed some of them into dopamine-making cells.
“The next steps to be taken toward achieving this goal include improving reprogramming efficiency, demonstrating the approach on human adult striatal astrocytes, developing systems to selectively target human striatal astrocytes in vivo, and ensuring safety and efficacy in humans,” the study concluded.
The study is a more sophisticated version of gene therapy approaches that have previously been investigated for Parkinson’s, and is worth pursuing, said Parkinson’s disease researcher Andres Bratt-Leal. However, much more work needs to be done before it can be considered for patients, he said. Meanwhile, other therapeutic projects are much closer to clinical testing.
Bratt-Leal is involved in one of those projects, a San Diego-based initiative to reprogram skin cells from Parkinson’s patients into embryonic-like cells called induced pluripotent stem cells, and then mature them into the dopamine producing neurons. These neurons will then be implanted into the brains of the patients, if work by the Summit for Stem Cell Foundation succeeds.
“Implanting new neurons has shown tremendous promise in animal models and clinical trials using dopamine-producing neurons derived from embryonic stem cells or induced pluripotent stem cells are going to start in the next 1 to 2 years,” said Bratt-Leal, the foundation’s director of research. “Gene therapy is promising, but there remain a lot of questions before it is ready for clinical trial.”
“In a dish, only a fraction of the cells are successfully made into cells which resemble dopamine-producing neurons,” Bratt-Leal said. “I'd like to know what happens to all the other cells which don't complete that transformation. Are the cells made with gene therapy as good as the neurons we can make from stem cells?”
“With cell therapy clinical trials around the corner and improvements in gene therapy technology, patients with Parkinson's disease have reasons to stay active and optimistic about the future.”

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