Newsbeat: Early ALS Treatment

Reprinted from PN/Paraplegia News February 2016

ALS gene can be reversed by therapies targeting the mutant gene responsible for the pathology recent study says

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Results from two independent research groups on an important new mouse model of an inherited amyotrophic lateral sclerosis (ALS) gene indicate that development of disease pathology precedes neurodegeneration, and can be reversed by therapies targeting the mutant gene responsible for the pathology. 

The studies were funded in part by The ALS Association.

ALS, also known as Lou Gehrig’s Disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure, and only one drug approved by the U.S. Food and Drug Administration modestly extends survival.

The two new studies were led by Jacqueline O’Rourke, PhD, and Robert Baloh, MD, PhD, both of Cedars-Sinai Medical Center in Los Angeles, and Owen Peters, PhD, Gabriela Toro Cabrera, and Robert Brown, MD, of the University of Massachusetts Medical Center in Worcester, Mass. 

Scientists have identified a mutation in a gene called “chromosome 9 open reading frame 72” or C9ORF72. This mutation results in six nucleotides, GGGGCC, being repeated up to 1,000 times within this gene in ALS patients. 

The two hypotheses that are most studied are that the mutated C9ORF72 makes mutated RNA transcripts (RNA is the molecule that usually helps DNA be translated into proteins) or makes unusual proteins called dipeptide repeat proteins (DRPs), each of which can aggregate, or clump, together and disrupt the normal activity of the neurons leading to neurodegeneration, says Cathy Seiler, PhD, program manager for the tissue biorepository at St. Joseph’s Hospital and Barrow Neurological Institute in Phoenix (read her science blog at

Both groups created a new model of C9ORF72 disease by inserting the gene carrying a large number of the expanded repeats into mice using a bacterial artificial chromosome, a genetic engineering tool specialized for carrying very large pieces of DNA. 

In each study, the mouse model was slightly different —  one had a mutated C9ORF72 with 500 GGGGCC repeats and the other varied between 100-1,000 repeats. However, both sets of researchers found the same results. 

In both studies, the mice had aggregated RNA transcripts and DRPs in their neurons just like what are found in human patients with ALS, but none of the mice had behavioral changes or neurodegeneration that are seen in human ALS patients, even at an advanced age. 

Environmental and/or genetic factors along with the aggregates caused by the C9ORF72 mutation must be involved in developing the neurodegeneration, the authors concluded. It may also mean that getting rid of these aggregates before neurodegeneration occurs may prevent development of ALS.


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