Common cause of ALS and a form of dementia found
Published Thursday, September 22, 2011 11:49AM EDT
Canadian researchers have helped discover a gene mutation that appears to link a common form of dementia to Lou Gehrig's disease.
The team from the University of British Columbia, working alongside researchers at the Mayo Clinic and elsewhere, say the mutation appears to link frontotemporal dementia to Lou Gehrig's, also called ALS or amyotrophic lateral sclerosis.
The mutation is certainly not the only cause of the fatal brain diseases, but the gene defect is the strongest genetic risk factor found so to date.
The discovery was made with the help of several British Columbia families that have high rates of FTD and Lou Gehrig's -- and sometimes both.
Frontotemporal dementia is the second most common form of early onset degenerative dementia. It strikes earlier in life than the better-known Alzheimer's disease, affecting adults between the ages of 45 and 65. Former Alberta permier Ralph Klein currently suffers from FTD.
Unlike Alzheimer's, which destroys a patient's memory, FTD shrinks the front lobes of the brain that control behaviour and speech. It causes personality and behaviour changes that some mistake for depression or a mid-life crisis.
Lou Gehrig's, or ALS, affects the brain in another way, destroying neuron cells that control muscles used for speaking, walking, and swallowing. It can lead to respiratory failure in as little as three years, though some patients, such as Stephen Hawking, can live with the illness for many years.
No cure exists for either disease and treatment options are few.
While the two diseases produce quite different symptoms, previous research has noted a link between the two. Up to half of ALS patients develop symptoms of FTD, and almost as many FTD patients show symptoms of ALS.
For this research, Dr. Ian Mackenzie, a professor in the department of pathology and laboratory medicine at UBC, provided samples or post-mortem brain tissue from a number of B.C. families with FTD or ALS or both.
The U.S. and Canadian teams worked together to zero in on a gene on chromosome 9, called C9ORF72. The gene encodes a protein whose role in disease is still not known.
They found an abnormally expanded repeat of two of the four nucleotides that make up the code in this gene. The DNA sequence repeats hundreds, and sometimes thousands, of times on the gene, leading to buildup of excessive DNA coding that seems to kill off affected brain cells.
After identifying the mutation, the Mayo researchers searched for it in patients with both familial and "sporadic" forms (uninherited) of the diseases.They found the mutation accounts for almost 12 per cent of familial FTD, and more than 22 percent of familial ALS samples they studied.
The defect is also the strongest genetic risk factor found to date for the more common sporadic forms of these diseases. It was found in 3 per cent of sporadic FTD and 4 per cent of sporadic ALS samples.
The findings are published in the journal Neuron.
It's hoped the finding will eventually lead to genetic tests, so that families with histories of either disease could get a better idea of their own risk of developing either disease.
It could also one day allow the development of new treatments and medications for both conditions.
Dr. Adam Boxer, of the Memory and Aging Center at University of California San Francisco, says the discovery is going to significantly improve the understanding of both diseases.
"We're actively trying to develop treatments for FTD, and we believe this discovery will pave the way for major advances in these efforts," he said in a news release.