Gene helps explain a third of inherited ALS cases

Wed Sep 21, 2011 1:09pm EDT

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By Julie Steenhuysen

CHICAGO, Sept 21 (Reuters) - Scientists have discovered a gene responsible for more than a third of inherited cases of amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, and a related brain disorder.

The findings, reported on Wednesday in the journal Neuron by two separate teams, could help scientists develop new animal models and may lead to new treatments for ALS and frontotemporal dementia, which are fatal neurological disorders.

The newly discovered mutation was found in almost 12 percent of people with familial fatal neurological disorders, known as FTD, and more than 22 percent of familial ALS studied, researchers at the Mayo Clinic in Florida reported.

The defect also is the strongest genetic risk factor found to date for the more common, non-inherited, sporadic forms of these diseases. It was found in 3 percent of sporadic FTD and 4 percent of sporadic ALS samples in the Mayo study.

"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," Rosa Rademakers, a Mayo Clinic neuroscientist who worked on the study, said in a statement.

In ALS, the disease kills nerve cells in the brain and spinal cord that control movement, leaving sufferers unable to move their arms, legs, body and eventually breathe without support. It is typically fatal three to five years after symptoms appear. About 5 percent of people with ALS have an inherited form of the disease.

FTD is the second most common form of early onset dementia after Alzheimer's. As the disease kills brain cells in the frontal lobe, it destroys people's ability to behave appropriately, empathize with others, learn, reason, make judgments, communicate and carry out daily activities.

The diseases are closely tied. About half of ALS patients have some symptoms of FTD, and about half of FTD patients have ALS symptoms. Both diseases can occur in the same family.

GENETIC STUTTER

Scientists said the newly discovered gene mutation is a bit unusual in that it repeats two of the four nucleotides that make up the genetic code hundreds to thousands of times, sort of like a genetic stutter.

They believe this rare genetic defect -- located on a single gene called C9ORF72 on chromosome 9 -- may be causing the chemical messenger RNA to latch on to certain proteins and develop clumps inside neurons that eventually kill the cells.

"We don't have a complete picture yet of how this leads to FTD and ALS but we have an exciting new direction in which to find out," Rademakers said in a statement.

Dr. Bryan Traynor of the National Institute of Health's National Institute on Aging, who led a separate study that identified the same genetic mutation, said the discovery means scientists can now explain nearly cases of familial ALS disease in Finland, which has the highest incidence of familial ALS and FTC worldwide.

He said the mutation is is present in more than a third of cases from patients in Italy, Germany, and North America.

Traynor and colleagues said the finding will allow them to develop a better mouse model to study the diseases.

"Finding these types of mutations is critically important to a better understanding of disease mechanisms, so that we can ultimately target disease biology to develop therapeutic interventions," he said in a statement. (Editing by Bill Trott)

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