Amyotrophic lateral sclerosis (ALS) could potentially be treated by targeting toxic RNAs
Scientists have reported a novel therapeutic approach for amyotrophic lateral sclerosis (ALS) by targeting the toxic RNA without affecting the normal RNA.
RNA refers to ribonucleic acid. It is a nucleic acid that contains the sugar ribose, is found in all living cells, and is essential for the manufacture of proteins according to the instructions carried by genes. RNA also acts instead of DNA as the genetic material in certain viruses.
ALS is also called as Lou Gehrig’s disease. It is a fatal degenerative disease of the nervous system marked by progressive muscle weakness and atrophy. It is a form of motor neuron disease and second most frequent dementia.
In 2011, researchers found that a specific gene known as C9orf72 is the most common genetic cause of ALS. Normally this gene has fewer than 30 of the nucleotide repeat unit, GGGGCC, but the mutant may contain hundreds of such repeat units producing repeat-containing RNAs i.e. toxic RNAs. Researchers found a number of changes in expression of other genes accompanying such mutation.
In the present research, scientists used the segments of genetic material called antisense oligonucleotides (ASOs) to block the accumulation of toxic RNAs that results in the most common form of ALS. This material does not affect the normal RNAs produced from the same gene.
“We reduced the accumulation of expanded RNA foci and corrected the sense strand of the gene. Importantly, we showed that we could remove the toxic RNA without affecting the normal RNA that encodes the C9orf72 protein. This selective silencing of a toxic RNA is the holy grail of gene silencing approaches, and we showed we had accomplished it,” said first author Clotilde Lagier-Tourenne, MD, PhD, UC San Diego Department of Neurosciences and Ludwig Institute for Cancer Research.
This research has not only potential for ALS but can also potentially be used to treat frontotemporal degeneration or frontotemporal dementia (FTD) that results in disturbances in behavior, personality, language and motor skills.
New Therapeutic Target Identified for ALS and Frontotemporal Degeneration – UC San Diego (http://health.ucsd.edu/news/releases/Pages/2013-11-08-new-target-for-ALS.aspx)
Clotilde Lagier-Tourenne et al. (2013). Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration PNAS DOI: 10.1073/pnas.1318835110