Antisense oligonucleotide (ASO) therapy is a new class of treatment of people with illnesses caused by defects in a single gene. In this novel approach, instead of repairing or replacing a gene function, the mutant gene is silenced, or perhaps just quieted. This is accomplished by delivering short single-stranded pieces of RNA that are engineered to bind to the RNA that would produce the mutant protein. Binding of the reverse sequence of RNA prevents transcription (ie, production) of the mutant protein.
Nusinersen (Spinraza; Biogen, Philadelphia, PA) is an ASO therapy approved for the treatment of persons with spinal muscle atrophy and is the first in this class of drugs to be approved. Phase 3 clinical trials of ASO therapy are underway for treating persons with Huntington’s disease.
Although there was promising safety data from a phase 1 clinical trial of an earlier ASO therapy treating persons with familial amyotrophic lateral sclerosis (ALS) the trial was discontinued in favor of developing more potent second generation ASO therapy. Now, researchers have shown that ASO directed at superoxide dismutase 1 (SOD1) extended survival and reversed muscle wasting in a mouse model of ALS (J Clin Invest. 2018 Jul 16.). The results suggest the newer version of the drug may be effective at treating inherited forms of ALS caused by mutations in SOD1. This data established the parameters for a phase 1 study that is currently underway (NCT02623699).Next Story