Sept. 21--Mayo Clinic researchers involved in a years-long, often frustrating search for a genetic mutation say they have discovered new information about the cellular roots of two diseases -- amyotrophic lateral sclerosis and frontotemporal dementia.
Mayo Clinic released the findings today in connection with publication of their research report in the online edition of Neuron.
"It's a very important discovery because now we have a new pathway we can study to try and identify potential targets for treatments for these patients," said senior investigator Rosa Rademakers, a neuroscientists at Mayo Clinic's Jacksonville campus. "It doesn't mean these treatments will be available tomorrow, but it will give us important new leads we can study further."
The genetic mutation is the most common cause discovered so far for ALS -- also known as Lou Gehrig's disease -- and frontotemporal dementia among patients who have a family history of the diseases, researchers said.
"Given that there are so many individuals who have this gene mutation, we hope that if it eventually leads to treatment, it will be something that benefits many patients," Rademakers said.
Mayo Clinic researchers in Jacksonville and Minnesota were joined by investigators from the University of British Columbia, the University of California San Francisco and the University of California Los Angeles on the study.
The genetic mutation is present at birth in people who have it. Rademakers said more research is needed to determine why the mutation leads to ALS for some people and frontotemporal dementia in others, why the disease emerges when people are adults, and why it strikes across such a broad range of ages.
Among ALS patients with a family history of the disease among close relatives, about 22 percent of those studied have the genetic mutation. For those with the dementia, about 12 percent have the genetic mutation if there is a family history, according to the study's results.
For those without a family history, 4 percent of ALS patients and 3 percent of dementia sufferers have the mutation. Researchers say it is the strongest genetic factor tracked down so far for people who don't inherit the risk for the diseases.
Kevin Boylan, head of the ALS Center at Mayo Clinic in Jacksonville, said the gene mutation offers another piece of information that's "pointing us in a slightly different direction to look at a disease mechanism that was not previously known."
The hunt involved a painstaking process of studying the highly complex world of genetic coding at the cellular level. A process of elimination narrowed the search using chemical reactions in the laboratory.
"We all realized how important it was to find it," Rademakers said. "But I must admit that over the years, we had periods when we just did not know how to go further because we basically had tried all the conventional methods and had not been able to find it."
She credits her laboratory assistant Mariely DeJesus-Hernandez with persisting in the testing and zeroing in on genetic area that was originally disregarded in the study.
That led to the discovery of a rare genetic defect. The mutation causes a short DNA sequence to repeat itself hundreds or thousands of times in people with the diseases, whereas it normally would repeat just two to 23 times.
David Bauerlein: (904) 359-4581
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