NEW insights into the mechanisms that cause amyotrophic lateral sclerosis (ALS) have been revealed by researchers from Stanford University, California, USA with the use of genome editing. The study not only increases understanding of how this neurodegenerative disorder progresses but could also provide the basis for new treatments.
Toxic Proteins
Previous research has shown that the gene C9orf72 is commonly a cause of ALS; its mutated form in ALS contains a large segment of DNA that repeats itself many more times than usual, which leads to the production of various toxic proteins that impede neuronal function and kill cells. In this study, the authors wanted to understand how the toxic proteins snuffed out healthy neurons and whether there were other genes that protect or otherwise exacerbate the effects of toxic proteins in the brain.
Genome-wide Screening
They used a method called genome-wide screening, which harnessed CRISPR-Cas9 gene-editing technology to ‘knock out’ genes, preventing them from carrying out their normal functions. This enabled the researchers to identify approximately 200 genes that either prevented or enhanced toxic proteins, finding a few that could potentially be utilised in the development of new drugs. One of these was a gene that normally codes the Tmx2 protein. When this gene was depleted in mouse neurons in a dish, the cells were able to survive at a rate of nearly 100%. This is in contrast to the survival rate for normal neurons, which was just 10%.
Therapeutic Target
“We could imagine that Tmx2 might make a good drug target candidate,” commented lead author Michael Haney. “If you have a small molecule that could somehow impede the function of Tmx2, there might be a therapeutic window there.”
The authors acknowledged that further work is needed to fully understand the role of Tmx2 in a cell and what functions are disturbed when the toxic proteins destroy the cell, before locating potential pathways.
Future Study
It is hoped that the genome-wide screening technique in this study could also be utilised to enhance understanding of the mechanisms of other neurological conditions, such as Alzheimer’s disease, in the future.
James Coker, Reporter
For the source and further information about the study, click here.
