Scots team's innovation may help to beat 'shocker of a disease'

BRAIN cells bearing a deadly genetic mutation linked to motor neurone disease have been created for the first time in an Edinburgh laboratory in a major breakthrough which could lead to a cure for the illness.

The stem-cell innovation marks the first significant step in a new offensive against the devastating condition whose victims include the celebrated astrophysicist Professor Stephen Hawking.

A University of Edinburgh team, including Dolly the Sheep cloning pioneer Professor Sir Ian Wilmut, transformed ordinary skin cells from patients into "tainted" motor nerves carrying the defect.

The scientists hope the work will provide new insights into how the disease develops, and allow the rapid screening of potentially therapeutic drug compounds.

Prof Wilmut said: "This is so much simpler a procedure, quite apart from the ethical issues.

"It's possible to take these cells, multiply them up to a very large number, and keep doing this for years, and to make these two types of cells, motor neurone and support cells.

"The funding from the MND Association will help us to understand why specific nerves die in motor neurone disease. This is a critical next step towards the ultimate goal of developing an effective treatment."

The Edinburgh scientists are key players in a new 800,000 research programme funded and launched today by the Motor Neurone Disease Association.

Others include teams led by Professor Chris Shaw at King's College London and Professor Tom Maniatis at Columbia University in New York.

Their main focus is on TDP-43, a gene mutation closely involved with motor neurone disease (MND).

Although it appears to be a direct cause in just 1 per cent of cases, the protein produced by the gene is found in the brains of up to 90 per cent of people with the disease.

This points to the mutation having a pivotal role in most types of MND that is not yet understood.

One of the chief aims of MND research was to find a simple way of studying the disease closely in a laboratory dish.

New stem cell technology has now made this possible by allowing scientists to manufacture large numbers of human cells with the TDP-43 gene.

Recently it was discovered that ordinary skin cells can be genetically tweaked to give them the properties of embryonic stem cells – potent "mother" cells, normally obtained from early stage embryos, with the ability to grow into virtually any kind of body tissue. Cells reprogrammed in this way are known as induced pluripotent stem (iPS) cells.

The Edinburgh scientists successfully produced iPS cells from skin cells donated by three patients and managed to transform them into TDP-43-bearing cells. Professor Siddharthan Chandran, a leading member of the Edinburgh team, described MND as a "shocker of a disease" for which there was no effective treatment.

The illness causes progressive muscle wasting and affects vital functions such as breathing and swallowing. It kills five people each day in the UK, with most victims living between two and five years. Half of those diagnosed die within 14 months.

The scientists hope the new research will at the very least lead to treatments which hold back progression of the disease.

"Being pragmatic I think slowing down the disease is the first aim, stopping the disease the second, and the home-run will be to restore function," said Prof Chandran.

Induced stem cells allowed the scientists to step out of the ethical minefield surrounding the use of human embryos and cloned animal-human hybrids as research tools.

Scientists at King's College will test the cells created in Edinburgh to see how they respond to injury, stress and over-stimulation.

The aim is to recreate environments which may help to trigger MND. The US collaborators will look for the genetic "signposts" of key biological processes in the cells which could provide useful drug targets.