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New Gene for Lou Gehrig's Disease Identified
Date:2/28/2008

Rare TDP-43 mutations expose potential therapeutic target, experts say

THURSDAY, Feb. 28 (HealthDay News) -- Researchers have implicated a new, yet rare, genetic mutation in the development of amyotrophic lateral sclerosis (ALS).

The finding not only exposes a potential therapeutic target for treating the fatal neurodegenerative disease, it also confirms that this particular mutation sets in motion the mechanism that causes many cases of ALS.

The results provide "a link between genetics and [the] pathology that proves that the pathology is important for the disease," said Virginia Lee, a professor of pathology and laboratory medicine at the University of Pennsylvania School of Medicine, in Philadelphia.

The results were published in the Feb. 28 online edition of Science.

ALS, also known as Lou Gehrig's disease, is an incurable motor neuron disorder that affects some 30,000 Americans, according to the ALS Association. From 5 percent to 10 percent of those cases are inherited; the remainder are sporadic. Several genes have been associated with the disease, most notably SOD1, which accounts for about 20 percent of familial cases and 3 percent of sporadic ones.

The gene in the present study, TARDBP, encodes TDP-43, a gene involved in, among other things, RNA processing. In 2006, Lee's group discovered that TDP-43 is a pivotal gene in both ALS and a cognitive disorder called frontotemporal lobar dementia (FTLD).

The question was, were these TDP-43 mutations involved in disease pathology or merely a byproduct of it?

"What we needed was a 'smoking gun,' " said Lee."Can we find mutations in TDP-43 in ALS patients?"

Dr. Christopher Shaw, a professor of neurology and neurogenetics at King's College London, led an international team of researchers to find out.

Shaw studied the TDP-43 gene in 154 families with familial ALS. They discovered one family wi
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