Stem cell model created for rare childhood disease

Scientists at the University of Wisconsin-Madison, US, have successfully created a human model for spinal muscular atrophy (SMA) by using the induced pluripotency technique (iPS cells) to grow large numbers of affected nerve cells which can be studied in the laboratory. Researchers can now observe the process by which SMA-affected cells are destroyed and use the cell model to screen potential treatments for effectiveness.

SMA is a neural degenerative disease affecting approximately one in 6,000 infants. It targets the neurons that control the muscles attached to the spine, causing weakness and paralysis and often resulting in early death. The researchers, who published their findings in the journal Nature, took skin cells from a young boy with a severe form of the disease and turned them into pluripotent cells. They then encouraged the cells to differentiate into neurons. As the neurons matured, they began dying, indicating that the model was active.

The team hopes to replay the process by which the cells die in order to understand the location of the damage and how to counteract it. Researchers predict that the ability to rapidly test potential therapies in the early stages of development will greatly facilitate the drug-discovery process. Clive Svendsen, who led the research team, explained that 'when scientists study diseases in humans, they can normally only look at the tissues affected after death and then try to work out how did that disease happen'. He added: 'It's a little like the police arriving at the scene of a road accident - the car's in the ditch, but they don't know how it got there'.

The creation of iPS cells involves manipulating adult cells so that they regress to a embryo-like pluripotent state. The technique was discovered by American and Japanese researchers in 2007. Pluripotent cells have the potential to become any one of the body's cell types. Until the discovery of induced pluripotency, it was thought that cells with this potential could only be found in the embryo. 'Now we can start from the beginning of development and replay the disease process in the lab dish,' Svendsen told Reuters in a telephone interview.

Under the new Human Fertilisation and Embryology Act, which selectively relaxes consent requirements for stored tissue samples, researchers in the UK will be able to use the cells of affected children to attempt human models of disease. The technique of deriving large numbers of affected cells for use in medical experimentation may not work for later-onset diseases such as Alzheimer's but should be effective for other early-onset conditions such as Huntington's disease. Dame Kay Davies, Professor of Anatomy at the University of Oxford, and leader of the team that first identified the defective gene causing SMA, described the new research as 'a very exciting breakthrough in progress towards a cure'.

It is hoped that so-called 'disease-in-a-dish' models will lead to better understanding and treatments for a wide range of conditions for which there are presently no good treatments and, in many cases, no good animal models.

Professor Robin Lovell-Badge, of the UK Medical Research Council's National Institute for Medical Research in London, told the BBC that the technique would undoubtedly become 'an important tool' for researchers. 'While I would be cautious about interpreting too much from this particular research, and would like to see it repeated using more stem cell lines, I expect this to fairly quickly become a significant aid to drug discovery,' he said.