Superoxide dismutase 1 pre-messenger RNA (SOD1 pre-mRNA)

Superoxide dismutase 1 (SOD1) pre-messenger RNA is the primary transcript of the SOD1 gene, which encodes a metalloenzyme responsible for converting superoxide radicals into molecular oxygen and hydrogen peroxide (UniProt P00441). While the mature protein is vital for antioxidant defense, mutations in the SOD1 gene lead to the production of misfolded proteins that aggregate and exert neurotoxic effects (PubMed: 32640123). This toxic gain-of-function is a major cause of familial Amyotrophic Lateral Sclerosis (ALS), a progressive neurodegenerative disease (NIH: Genetic and Rare Diseases Information Center). SOD1 pre-mRNA has emerged as a key therapeutic target, specifically for antisense oligonucleotides (ASOs) designed to reduce the expression of the toxic protein. Drugs like Tofersen bind to the SOD1 pre-mRNA, facilitating its degradation by RNase H before it can be translated into protein (FDA: Qalsody Prescribing Information). By lowering the levels of SOD1 pre-mRNA, these therapies aim to decrease the concentration of SOD1 protein in the central nervous system, potentially slowing disease progression. Clinical monitoring of this target often involves measuring SOD1 protein levels and neurofilament light chain (NfL) in the cerebrospinal fluid as markers of target engagement and axonal damage (Miller et al., 2022, NEJM).

Other names

Superoxide dismutase [Cu-Zn] pre-mRNASOD1 precursor mRNASOD1 transcript

Antisense oligonucleotide-mediated RNase H-dependent degradation of pre-mRNA to reduce protein expression