Nature (July 2011), DOI:10.1038/nature10284.
Vania Broccoli et al. “Direct generation of functional dopaminergic neurons from mouse and human fibroblasts”.
Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1105135108
Malin Parmar et al. “Direct conversion of human fibroblasts to dopaminergic neurons”.
People with Parkinson’s disease might one day be treated with brain cells made from their own skin.
Two teams of researchers have independently worked out how to turn skin cells into specialised neurons that make dopamine. This neurotransmitter, which is vital for mobility, is depleted in the brains of people with Parkinson’s.
The studies raise the possibility of improving mobility in people with Parkinson’s by restoring dopamine production to normal. At present, most patients take a drug called L-dopa to readjust levels, but with varying levels of success.
Both techniques avoid the initial step of converting skin cells into embryo-like pluripotent cells – a technique which poses a possible cancer risk.
Vania Broccoli of the San Raffaele Scientific Institute in Milan, and colleagues, first reprogrammed mouse skin cells using three transcription factors – proteins previously linked with the development of the neurons. The same trio of factors transformed skin cells taken from human embryos, healthy adults and people with Parkinson’s.
Infect skin cells
The only drawback is that Broccoli’s team first had to infect the skin cells with viruses carrying genes to make the transcription factors, although the viruses used are not ones that might disrupt DNA and cause cancer.
The Swedish team at Lund University, led by Malin Parmar, first converted human skin cells from embryos into neurons, then into specialised ones that make dopamine. Altogether, they used five transcription factors, including two used by the Italians – Mash1 and Lmx1a.
Broccoli says his team is testing whether neurons created from mouse cells benefit mice and rats bred to have a Parkinson’s-like disease. “Our goal is to use mouse cells first, then human cells in mice,” he says. “If this works, we’ll move to monkey models of the disease.”
His team is also evaluating methods of reprogramming skin cells that might dispense with viruses, to eliminate any potential risks viruses might pose to human recipients. “We’re actively analysing this, but have no hard data yet,” he says.
And in Sweden, Parmar says that similar experiments are under way to test whether her team’s human cells benefit animals with the disease. “We must prove these are functional in vivo,” she says.