Breakthrough on ALS treatment seen

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WORCESTER, Massachusetts: An international team of researchers has moved a step closer to understanding the crippling, fatal disease amyotrophic lateral sclerosis, or ALS.

Research led by John Landers, a PhD at the University of Massachusetts (UMass) Medical School, and medical doctor Bryan Traynor at the National Institute on Aging at the National Institutes of Health, has identified a new gene, KIF5A, associated with the development of ALS. KIF5A is one of a growing list of gene mutations found in ALS patients.

The discovery was published in the journal Neuron.

“It opens the door to developing new models for the disease,” Landers said.


ALS is a progressive neurodegenerative disease that affects neurons in the brain and spinal cord. People with
ALS slowly lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis.

Only 10 percent of people diagnosed with ALS live more than 10 years after diagnosis, according to Landers.

English physicist Stephen Hawking died on March 14 at age 76, after having been diagnosed with ALS in his 20s. He was one of the longest-living people with the disease.

More than 200 researchers participated in the current study, analyzing the genetic profiles of more than 100,000 people.

The research further implicates the role of defects in the cytoskeleton, the structure in cells that helps transport proteins and electrical impulses from one part of the cell to another, in development of ALS.

Landers explained the cytoskeleton is like a railroad track. The gene KIF5A works to move material up and down the track. When there are defects, or mutations, in KIF5A, nerve messages can’t be successfully communicated.
KIF5A is also connected to defective RNA processing found in ALS.

Focused on the therapeutic

Landers said KIF5A “is an area that should be focused on as therapeutic” in the search for a cure.

KIF5A mutations are also linked to a rare form of another disease, hereditary spastic paraplegia, or HSP, a slowly progressive neurodegenerative disease.

People who have ALS with the KIF5A mutation tend to develop the disease at a younger age, but live an average of 10 years, compared to the typical survival of two to three years for people with other mutations linked to ALS, according to Landers.

Researchers tackled the analysis through two different approaches. NIH scientists looked at genetic sequences among the 90 percent of people with ALS who have no known family history of the disease, which is known as sporadic origin.

The UMass-led team looked at the 10 percent of ALS cases in which there is a family history. They found mutations that shorten the gene protein.

Both approaches identified KIF5A as a novel gene associated with ALS.

Next steps for research include developing mouse models, understanding the differences between mutations that cause HSP and those that cause ALS, using stem cells, and testing for small compounds or genes that could repair a KIF5A mutation, Landers said.

While there are therapeutic treatments in the pipeline that “seem to be very, very promising” for familial ALS, Landers said, finding successful treatment for sporadic ALS, where there isn’t a genetic history, is less easy.

Still, he said, when he started working on ALS research 15 years ago, he told his parents there was “absolutely nothing” in sight for a cure. Now, he said, “There’s a dramatic difference. I’ve seen some major leaps in 15 years.”

Funding from the ALS Association, which includes proceeds from the Ice Bucket Challenge, was instrumental for this project, according to Landers. “This study represented the largest collaborative genetics efforts in ALS.

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