A Stanford Medicine-led team of researchers has developed an approach for targeting and blocking the expression of a protein thought to contribute to the development of amyotrophic lateral sclerosis, a progressive neurodegenerative disease in humans.
They developed a treatment for mice genetically predisposed to an ALS-like illness. The new treatment did not cure sick mice, but it dramatically slowed the onset and progression of the disease in mice that were treated at birth before symptoms appeared.
ALS is a disease in which the nerve cells in the brain and spinal cord degenerate, leading to wasting of the muscles. Patients gradually lose the ability to move, speak, eat and breathe, often leading to paralysis and death within two to five years. Many aspects of the disease remain little understood, however one indication of the disease is the development of clumps of the protein TDP-43 in the brain. Yet TDP-43 is essential for cells, so it doesn't make a good therapeutic target.
Researchers had previously found that when they remove a second, nonessential protein, called ataxin 2, cells are more able to resist the deleterious effects of the TDP-43 clumps.
The new treatment blocks the production of ataxin 2. Mice without ataxin 2 lived up to 10 times longer than untreated mice. Treated mice scampered normally while untreated mice coped with ALS-like paralysis.
A paper describing the work appears today in Nature. Aaron Gitler, PhD, associate professor of genetics, is the senior author and Lindsay Becker, a graduate student, is lead author.
As explained in our news release:
'We wanted to find out if we could protect these mice from the consequences of TDP-43 by lowering the amount of ataxin 2,' said Gitler. Becker genetically engineered these ALS mice to have half the normal amount of ataxin 2, and also engineered other mice to completely lack the protein. She found that with half the ataxin 2, the ALS-like mice survived much longer. 'But what was really astounding,' said Becker, 'was that when we completely removed ataxin 2, there was really an unprecedented survival; some of the mice lived hundreds and hundreds of days.'
Gitler's team next tried something that could have a more direct therapeutic value: treating mice with a type of DNA-like drug, designed to block the production of ataxin 2...
Whether the treatment can reverse or slow the disease once symptoms appear is unknown; finding out is next.
Previously: Pure brainpower directs onscreen cursor, letting paralyzed people type, Quest for molecular cause of ALS points fingers at protein transport, say Stanford researchers, Stanford researchers provide insights into how human neurons control muscle movement
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