Mutant ALS (amyotrophic lateral sclerosis) gene C9ORF72 may be suppressed using a short, synthetic chain of chemically modified nucleotides (antisense oligonucleotide, ASO) as per a pilot human study at the University of Massachusetts Medical School, published in Nature Medicine.
ALS is a degenerative condition where the brain and spinal cord nerve cells are attacked progressively,
thereby affecting the individuals’ ability to move, speak, eat, and even breathe.
‘Mutant ALS (amyotrophic lateral sclerosis) gene C9ORF72 may be suppressed using a newly engineered, short, synthetic chain of chemically modified nucleotides (antisense oligonucleotide, ASO).’
The mutant C9ORF72 gene is known to be the most common cause of familial amyotrophic lateral sclerosis (ALS) and familial frontotemporal dementia (FTD).
The team found that injecting ASO into the spinal canal had led to a significant reduction of ALS-related neurotoxins known as dipeptide repeat proteins (DPRs) in the trial participants. The engineered nucleotides thereby hold the potential to catalyze further treatments options for ALS, FTD, and other neurodegenerative diseases.
“The results are very encouraging. It means this is a viable approach to suppressing the mutant C9ORF72 protein that causes most cases of familial ALS. The next step is to launch a multi-person clinical trial to see if this treatment can slow progression of the disease,” says Dr. Brown, the Leo P. and Theresa M. LaChance Chair in Medical Research, and professor of neurology at UMass Chan Medical School and lead author of the study.