Cells similar to dopamine neurons - a cell type that is lost in Parkinson’s disease - can be created by treating non-neuronal brain cells with a specific combination of molecules, according to a study published online this week in Nature Biotechnology. The new reprogramming method is demonstrated both in cultured human cells and in a mouse model of Parkinson’s disease.
A defining feature of Parkinson’s disease is the progressive death of a specialized type of neuron that secretes dopamine. Although several treatments are available to patients, including a drug that is a chemical precursor of dopamine, none change the course of disease. A decades-long research effort is seeking to develop a disease-modifying therapy in which dopamine neurons or their precursors would be generated in the laboratory and transplanted into the brain.
Ernest Arenas and colleagues describe a different approach to cell replacement that does not require cell transplantation. By testing a number of genes known to be important for dopamine-neuron identity, they identified four genes that, when combined with certain small molecules, reprogram human brain cells called astrocytes into cells that resemble dopamine neurons.
To study the strategy’s therapeutic potential, the authors used a toxin to kill dopamine neurons in mice and then delivered the four genes to the brain using a system designed to express the genes only in astrocytes. Some astrocytes were successfully reprogrammed, acquiring characteristics of dopamine neurons and correcting several behavioral symptoms caused by dopamine-neuron loss. Substantial further research would be needed before this approach could be considered for human trials, the authors note.
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