Motor neuron disease breakthrough
By Roger Highfield, Science Editor
Last Updated: 7:01pm GMT 28/02/2008
A breakthrough in understanding motor neuron disease, the incurable degenerative disorder, has been made by scientists.
The world's best known scientist, Prof Stephen Hawking, is a sufferer of the devastating disorder. Now an international effort led by King's College London reports in the journal Science that it has identified a rare mutation associated with some cases that they believe reveals the underlying mechanism that causes the disease for the first time, a key step towards developing effective treatments.
Deposits of an abnormal protein now appear central to the processes that trigger the dying neurons characteristic of the disease, also called amyotrophic lateral sclerosis (ALS), linking it to other ones marked by abnormal proteins, notably Parkinson's, variant CJD and Alzheimer's disease.
To make the find, Prof Chris Shaw, Jemeen Sreedharan and colleagues in the United Kingdom and Australia analysed a large British family with the inherited form of the disease. They found mutations in a gene called TDP-43 that can directly cause the disease.
Clumps of the TDP-43 protein accumulate within dying motor neurons. This discovery indicates that TDP-43 accumulation is not just a by product of nerve degeneration - as some had thought - but may be a critical event that is central to the disease process.
At the moment, doctors do not know the cause of over 95 per cent of cases of the disease, though they do know that genetic factors play an important role. Because drugs based on the only other gene linked to the disease, called SOD, had failed to have any beneficial effect in patients scientists had been searching for a new clue to the cause.
TDP-43 is depositied in 95 per cent of patients and although TDP-43 gene mutations are rare they do give us a potentially powerful biological tool. "If we can use the mutant human gene to generate cellular and animal models of MND we have a real chance of understanding how motor neurons degenerate. This could dramatically accelerate the drug screening process", says Prof Shaw.
Prof Shaw said the find opens "fantastic opportunities" and is now going to create human stem cells containing the mutation with Sir Ian Wilmut of Edinburgh University, which will be an invaluable tool to simulate, understand and test treatments for the devastating disease.
The disease attacks the upper and lower "motor neurons", causing weakness and wasting of muscles, increasing loss of mobility in the limbs and difficulties with speech, swallowing and breathing. It can affect any adult at any age but most people diagnosed with the disease are over the age of 40, with the highest incidence occurring between the ages of 50 and 70.
The incidence or number of people who will develop the disease each year is about two people in every 100,000. The prevalence or number of people living with MND at any one time is approximately seven in every 100,000.
Brian Dickie, director of research development at the MND Association, which partly funded the study, said: "The discovery of a new cause of the disease is of international importance, allowing researchers around the world to rapidly generate more pieces of the complex puzzle that is MND.
"This new information will be a spring board to greater understanding of the processes that cause motor nerves to die - and it is through such understanding that we will develop the treatment strategies to defeat this devastating disease."
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