Study sheds light on paralysing ALS

Researchers have discovered a genetic mutation that causes a paralysing illness called ALS in some people, a finding they said on Thursday may lead to treatments for the degenerative nerve condition.

Their study showed how this genetic variation produced proteins that were toxic and killed motor neuron cells in people with amyotrophic lateral sclerosis or ALS, also commonly known as motor neuron disease or Lou Gehrig's disease.

"We discovered that the mutation was appearing only in people who were affected," said Chris Shaw, a researcher at the Institute of Psychiatry in London who led the study published in the journal Science. "This suggested it is disease-causing."

The finding is important, he said, because the disease kills quickly - usually between two and five years after symptoms start - and has no effective treatments. Physicist Stephen Hawking is a rare example of a person who has survived for years with the condition.

ALS leaves people unable to walk, talk or feed themselves but does not usually affect their intellect and other senses. Doctors diagnose about 120,000 new cases each year, according to the International Alliance of ALS.

Shaw and colleagues isolated a mutation in a gene called TARDBP in people with a rare, inherited form of ALS. They found that people with this variation produced a mutant and toxic protein called TDP-43.

Previous research had suggested the protein might have existed as sort of cellular junk generated as a harmless by-product of the disease. But by injecting these mutated proteins into the spines of chicks in eggs, Shaw's team showed they actually killed motor neurons.

While only about 1 percent of people have this form of ALS, the findings have wider implications because most people with the disease have these proteins accumulating in the wrong place within the cell, Shaw said.

"It also means we develop new and better disease models, which will bring us close to developing more effective therapies," he said.

In 1993 a group of U.S. researches identified a gene called SOD1 that caused a form of ALS affecting about 5 percent of people with the disease - the only people with the condition who do not accumulate TDP-43 proteins, Shaw said.

That finding triggered a flood of new research into the disease, and the discovery of a second gene could draw even more people into the field, said Brian Dickie, director of Research Development at the Motor Neuron Disease Association.

"The discovery of a new cause of the disease is of international importance, allowing researchers around the world to rapidly generate more pieces of the complex puzzle that is motor neuron disease," he said.