British scientists have launched the world's first stem cell project to recreate a devastating and incurable brain disease in the laboratory. The team, led by Sir Ian Wilmut, the Edinburgh researcher who cloned Dolly the sheep, will use stem cells to make diseased and healthy brain cells to study how motor neurone disease progresses into a lethal condition. The research, which will give scientists unprecedented insight into a disease that is almost impossible to study in living patients, could be the best long-term hope doctors have for finding treatments for the condition.
In motor neurone disease (MND), brain and spinal cord nerves that control muscles steadily die off, leaving patients trapped in a body that becomes increasingly useless. People become paralysed, unable to talk or eat, and often can only breathe with aid from a mechanical ventilator.
Around half of all MND patients die within three years of being diagnosed. Five people die every day from the condition in Britain. One of the longest-living survivors of the condition is Stephen Hawking, the 68-year-old cosmologist, who was diagnosed at the age of 21.
Wilmut's team at Edinburgh will work with scientists in London and New York to understand how the disease kills off nerve cells and spreads itself to healthy parts of the brain and central nervous system.
The project represents a refinement of plans to use controversial "hybrid embryos" to create stem cells that carry a genetic mutation responsible for motor neurone disease. With hybrid embryo technology, a skin cell from a disease-carrying patient is fused with an animal egg to form an early-stage embryo. Stem cells can be collected from these embryos and grown into adult nerve cells that are prone to developing the disease.
Many scientists have abandoned plans to use hybrid embryos in favour of a simpler and less controversial technique, in which adult skin cells are chemically reprogrammed into a stem cell-like state, so called induced pluripotent stem (iPS) cells. Wilmut's team has already taken skin cells from patients with a rare genetic mutation that causes motor neurone disease and converted them into iPS cells. They grew these in Petri dishes into two kinds of adult nerve cells, and did the same with skin cells from healthy people.
The GBP800,000 project, funded by the Motor Neurone Association, will investigate how the brain cells grow, and in particular will examine why those carrying the genetic mutation die off. Understanding what goes wrong will give scientists a clue as to how to slow and even stop the disease. Drugs that may show promise in slowing or stopping the condition can be tested by adding them directly to the disease-carrying brain cells in the lab. "Slowing down the disease is our first aim, stopping the disease is the second, and the home run would be to repair and restore lost function," said Prof Siddharthan Chandran, a member of the Edinburgh University team.
The patients in the study carry a mutation in a gene called TDP43. Although the gene is thought to cause only 1% of cases directly, the mutation is linked to changes seen in 90% of patients with the disease.
One question the researchers will try to answer is how the disease spreads from one part of the brain to another. Colin Blakemore, president of the MND Association, said: "There is great hope that this approach will enable us to unravel the mystery of motor neuron disease: why and how particular nerve cells die."
