Tofersen (BIIB067) is an Antisense Oligonucleotide for Amyotrophic Lateral Sclerosis Research

SOD1 (superoxide dismutase 1) is an important antioxidant enzyme. It scavenges harmful free radicals in cells and protect neurons from oxidative stress damage. However, mutations in the SOD1 gene can lead to abnormal structure of the SOD1 protein. Thus, mutant protein in turn causes neuronal degeneration and death. Moreover, Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. And SOD1 gene mutation is closely related to the progression of ALS and is a key target of ALS. Particularly, antisense oligonucleotide (ASO) can directly target mRNA and inhibit the production of target protein. Here is an antisense oligonucleotide inhibitor of SOD1, Tofersen (BIIB067), which can mediate the degradation of SOD1.

Tofersen (BIIB067) mediates RNase H-dependent degradation of superoxide dismutase 1 (SOD1) mRNA.

As an ASO, Tofersen binds to SOD1 mRNA through complementary base pairing. Specifically, Tofersen activates RNase H1 thereby destroying target RNA. Meanwhile, SOD1 locates assumedly in the outer mitochondrial membrane (OMM), and its genetic mutation leads to abnormal protein aggregation, resulting in oxidative damage to mitochondria and other organelles, thereby accelerating neuronal degeneration and the progression of ALS. Finally, Tofersen reduces the synthesis of SOD1 protein and mediates its degradation. Illustrates its inhibitory potential in ALS.

On another hand, ASO has been widely used in the research of central nervous system diseases. As approved in Huntington’s disease, SOD1-related ALS, Alzheimer’s disease. SOD1 ASOs have also grown considerably in rodent models. In summary, Tofersen is a potent antisense oligonucleotide inhibitor that inhibits the production of SOD1. In addition, it has potential in the research of amyotrophic lateral sclerosis.


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