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Same genetic mutation linked to ALS and dementia

26 September 2011
Appeared in BioNews 626

Researchers have identified a strong link between a genetic fault and two common neurological disorders. Two independent studies have found that the mutation is common in patients with amyotrophic lateral sclerosis (ALS) and patients with frontotemporal dementia (FTD), particularly if the disease is familial.

Researchers believe that the genetic abnormality in the C9ORF72 gene is the most common cause of the fatal disorders, and hope that it will provide more information about the link between ALS and FTD. The discovery provides insights into how the diseases develop and could help to find future treatments.

Published in the journal Neuron, the studies both found that a DNA sequence on chromosome 9, usually only repeated two to 23 times, is repeated hundreds, or even thousands of times in a large proportion of patients with ALS and FTD. Previous work had identified a link between both diseases and this region of chromosome 9, but the specific mutation had not been identified until now.

'This finding has the potential to lead to significant insights into how both of these neurodegenerative diseases develop, and may give us much needed leads into new ways to treat our patients', said Dr Rosa Rademakers of the Mayo Clinic in Florida, who led one of the studies.

Her research looked at patients in the US and Canada, finding that the mutation was present in 24 percent (%) of familial ALS patients and in 12% of familial FTD patients. For sporadic ALS and FTD, it was found in 4% and 3% of patients respectively.

The second study, led by Dr Bryan Traynor of the National Institute on Aging in Maryland, looked at hundreds of patients in Finland, where ALS is more common than in other western countries. They found the mutation in 46% of patients with familial ALS, and in 21% with sporadic ALS.

'In terms of thinking of the future, what this provides us with is a target to go after', Dr Traynor said. 'What this allows us to do is to design cell models and animal models of disease we can use to start to screen drugs and therapeutic agents to see if they are effective in turning off this particular genetic mutation'.

ALS, also known as Lou Gehrig's disease, causes a breakdown of the nerve cells in the brain and spinal cord, eventually resulting in paralysis. The patients eventually lose the ability to breathe, and usually die within five years of diagnosis. FTD is the second most common form of early onset dementia, after Alzheimer's disease. The disease kills cells in the brain's frontal lobe, causing a number of neurological symptoms. Eventually, as cognitive abilities decrease, patients are no longer able to care for themselves or perform simple everyday tasks.

Both diseases are known to be hereditary – 10% of ALS and 50% of FTD cases are familial according to Cell Press – and four genes have already been linked to their development, accounting for about 25% of familial ALS cases. The newly discovered gene, located on the chromosome region 9p21, is said to account for a further 40% of cases.

Despite the differences in the diseases' symptoms, researchers had previously known of a link between them – according to Reuters, about half of ALS patients have some symptoms of FTD, and about half of FTD patients have some ALS symptoms.

Dr John Trojanowski, from the University of Pennsylvania, whose research previously identified links between the diseases, told Science magazine: 'This is a big step forward because it's such a common mutation. These findings add further compelling evidence to the concept ... that ALS and [FTD] are mechanistically related disorders at either ends of a clinical and pathological spectrum'.

However, despite the new findings, researchers still do not know how the mutations cause either disease, or why some individuals with the mutation develop ALS, and others FTD.

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