Neuron breakthrough offers hope on Alzheimer’s and Parkinson’s

http://www.timesonline.co.uk/tol/news/science/medicine/article7005401.ece

Hannah Devlin

From The Times
January 28, 2010

Neurons have been created directly from skin cells for the first time, in a remarkable study that suggests that our biological makeup is far more versatile than previously thought.

If confirmed, the discovery that one tissue type can be genetically reprogrammed to become another, could revolutionise treatments for conditions such as Parkinson’s disease and Alzheimer’s, opening up the possibility of turning a patient’s own skin cells into the neurons that they need.

The study by scientists from Stanford University, California, also suggests that skin cells could be reprogrammed to provide a limitless supply of blood or bone marrow for personalised transfusions.

Until now, the consensus was that only master cells from embryos, or adult cells that have been ‘rewound’ into an embryo-like state — a process that takes several weeks — have the ability to form all the different types of tissue in the body.
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The latest study, carried out in mice, reveals that while cells choose and maintain their speciality during the earliest phase of development, they retain an underlying flexibility. Provided that the correct genes are turned on or off they could potentially be turned into any other variety of tissue in the body.

The work has been hailed as a huge conceptual leap forward in fundamental biology. “The possibility that cells could be directly reprogrammed is something that people had thought about, but to see it in black and white is still slightly shocking,” said Professor Jack Price, a neurobiologist at King’s College London. “This suggests that there are no great rules — you can reprogramme anything into anything else.”

The finding will address some of the ethical objections of groups who oppose embryonic stem-cell research, in which the embryo is destroyed. And the new process is much quicker than the alternative method, where adult cells are “rewound” to create versatile master cells, known as induced pluripotent stem (iPS) cells.

In the study, published in the journal Nature, skin cells were infected with a genetically modified virus that inserted genes into the cells’ DNA. The researchers began by introducing 19 genes that are known to be switched on when mice stem cells first differentiate into neurons during embryonic development.

Using a mix-and-match approach, the researchers found that of the 19 genes initially tested, only three were truly necessary to get the skin cells to develop into neurons. When these three genes were switched on, 20 per cent of the skin cells had turned into fully functioning neurons in less than a week. The neurons were able to make connections with and signal to other nerve cells — critical functions if the cells are eventually to be used as therapy for Parkinson’s disease or other disorders.

“We were very surprised by both the timing and the efficiency,” said Irving Weissman, a stem cell expert at Stanford University in California, who led the research. "This is much more straightforward than going through iPS cells, and it’s likely to be a very viable alternative.”

In terms of clinical applications, a further advantage of skipping out the intermediate iPS state is that it is known that iPS cells promote cancers. Many researchers believe it would be difficult to obtain a license for the use of cells that are grown from iPS cells.

“People have been saying that iPS cells could be used therapeutically in the near future, but frankly they’ve been lying,” said Professor Price. “These cells don’t go through a tumourigenic phase, which means it would be much easier to get a licence to use them.”

The Stanford group are now working to reproduce the finding using human cells, but say that there is no reason to expect it should not apply to most species.

A further question is why, if cells retain an underlying versatility, they don’t switch between cell types throughout our life. One possible explanation is that genes interact via “see-saw” mechanisms, whereby when one set of genes are switched on, they automatically keep other genes switched off unless an artificial intervention is made.