A second generation drug may prove effective in treating an inherited form of amyotrophic lateral sclerosis (ALS), according to a study by the National Institute of Neurological Disorders and Stroke, a part of the National Institutes of Health.
The findings of the study, published in the Journal of Clinical Investigation, found that newer versions of a gene therapy, called antisense oligonucleotide, delayed the signs of ALS in rodents by silencing the gene, superoxide dismutase 1 (SOD1).
Prior research found that older versions of an antisense oligonucleotide were able to turn off a form of ALS caused by mutations in SOD1, according to the authors of the current study. The treatment was found to attach to versions of the gene encoded in messenger RNA (mRNA), mark the genes for disposal, and stop the production of the SOD1 protein.
The researchers used a newer version of an antisense oligonucleotide previously tested in a phase 1 trial to treat rodents genetically modified to carry normal or disease-mutant versions of human SOD1. They found that the infusion of newer versions of the drug was more efficient in decreasing normal, human SOD1 mRNA levels in rats and mice.
The drug was also found to extend survival in rats that were genetically modified to carry a disease-causing mutation of SOD1 compared with an older version of an antisense oligonucleotide, according to the study.
The new formulation of the antisense oligonucleotide was also found to delay the age that mice carrying the mutant SOD1 gene began to have difficulty balancing on a rotating rod. The researchers also found that the drug apparently prevents muscle weakness and the loss of nerve and muscle connection.
Based on these findings and the belief that the next generation drug could help treat muscle activation problems in patients with ALS, the antisense oligonucleotide will be evaluated in a phase 1 clinical trial in patients with the disease.