Few diseases are as terrifying as Huntington's, an inherited genetic disorder that gradually saps away at sufferers' muscle control and cognitive capacity until they die (usually some 20 or so years after initial symptoms). But scientists at Washington University School of Medicine may have provided a new glimmer of hope by converting human skin cells (which are much more readily available than stem cells) directly into a specific type of brain cell that is affected by Huntington's.
This new method differs from another technique devised at the University of Rochester last year in that it bypasses any intermediary steps rather than first reverting the cells to pluripotent stem cells, it does the conversion in a single phase.
To reprogram the adult human skin cells, the researchers created an environment that closely mimics that of brain cells. Exposure to two types of microRNA, miR-9 and miR-124, changes the cells into a mix of different types of neurons. "We think that the microRNAs are really doing the heavy lifting," said co-first author Matheus Victor, although the team admits that the precise machinations remain a mystery.
Huntington's disease especially affects medium spiny neurons, which are involved in initiating and controlling movement and can be found in a part of the basal ganglia called the corpus striatum. This part of the brain also contains proteins called transcription factors, which control the rate at which genetic information is copied from DNA to messenger RNA.
By exposing human skin cells (top) to a combination of microRNAs and transcription factors, the researchers were able to create medium spiny neurons (bottom) (Image: Yoo Lab/Washington University at St Louis)
The researchers fine-tuned the chemical signals fed into the skin cells as they were exposed to the microRNAs, with the transcription factors guiding the cells to become medium spiny neurons. Different transcription factors would produce different types of neurons, they believe, but not without the microRNAs which appear to be the crucial component, as cells exposed to transcription factors alone failed to become neurons.
When transplanted into the brains of mice, the converted cells survived at least six months while showing functional and morphological properties similar to native neurons. They have not yet been tested in mice with a model of Huntington's disease to see if this has any effect on the symptoms.
The research will nonetheless contribute to scientific understanding of the cellular properties associated with Huntington's, regardless of whether this new method leads directly to a treatment or cure.
A paper describing the research is available in the journal Neuron.
Source: Washington University in St Louis
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Converting skin cells directly into brain cells advances fight against Huntington's disease
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