Scientists have developed a new way to ramp up the conversion of skin cells into dopamine neurons which are lost in Parkinson's, an advance that could lead to new treatments for the disease.
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For decades, the elusive holy grail in Parkinson's disease research has been finding a way to repair faulty dopamine neurons and put them back into patients, where they will start producing dopamine again.Making dopamine neurons from stem cells is a long process with a low yield. These issues have driven researchers to try to develop ways to turn cells that are easy to obtain, such as skin cells, into dopamine neurons, which are normally hidden in the brain. But it has been difficult to obtain sufficient quantities of neurons.
Now, researchers at the University at Buffalo have developed a way to ramp up the conversion of skin cells into dopamine neurons.
They have identified - and found a way to overcome - a key obstacle to such cellular conversions.
The new research, revolves around their discovery that p53, a transcription factor protein, acts as a gatekeeper protein.
"We found that p53 tries to maintain the status quo in a cell, it guards against changes from one cell type to another," said Jian Feng, senior author and professor in the Jacobs School of Medicine and Biomedical Sciences at UB.
"We found that p53 acts as a kind of gatekeeper protein to prevent conversion into another type of cell. Once we lowered the expression of p53, then things got interesting: We were able to reprogramme the fibroblasts into neurons much more easily," said Feng.
"This is a generic way for us to change cells from one type to another," he said.
"People like to think that things proceed in a hierarchical way, that we start from a single cell and develop into an adult with about 40 trillion cells, but our results prove that there is no hierarchy," he said.
"Our method is faster and much more efficient than previously developed ones," said Feng.
"The best previous method could take two weeks to produce 5 per cent dopamine neurons. With ours, we got 60 per cent dopamine neurons in ten days," he said.
The researchers have done multiple experiments to prove that these neurons are functional mid-brain dopaminergic neurons, the type lost in Parkinson's disease.
The finding enables researchers to generate patient-specific neurons in a dish that could then be transplanted into the brain to repair the faulty neurons.
It can also be used to efficiently screen new treatments for Parkinson's disease.
The study was published in the journal Nature Communications.
