Tofersen sodium  (Synonyms: BIIB067 sodium; ISIS-SOD1Rx sodium; ISIS 333611 sodium)

Tofersen (BIIB067) sodium is an antisense oligonucleotide and SOD1 mRNA inhibitor with an IC₅₀ of 320 pM. Tofersen sodium mediates RNase H-dependent degradation of SOD1 mRNA to reduce SOD1 protein levels in cerebrospinal fluid and serum. Tofersen sodium downregulates cerebrospinal fluid neurofilament light chain, neurofilament heavy chain, amyloid-beta 1-40, amyloid-beta 1-42, neuropeptide Y, ubiquitin C-terminal hydrolase L1, neuropentraxins 1, 2, R, corticotropin-releasing hormone, IL-15, and serum neurofilament light chain, neurofilament heavy chain. Tofersen sodium can be used for the research of superoxide dismutase 1-associated amyotrophic lateral sclerosis^{[1][2][3][4][5][6][7][8][9]}.

Tofersen (72 h) sodium potently silences SOD1 mRNA in human HeLa cells with an IC₅₀ of ~0.32 nM^[2].
Tofersen sodium-loaded Ca²⁺P lipid nanoparticles (72 h) reduce SOD1 protein levels by >3.3-fold in HEK293T cells after 72 h of incubation^[5].
Tofersen sodium-loaded Ca²⁺P lipid nanoparticles (0.78-50 nM; 1-48 h) exhibit dose- and time-dependent uptake into NSC-34 mouse motor neuron-like cells, are non-cytotoxic at concentrations up to 25 nM after 48 h, and undergo pH-dependent release of Tofersen within the cytoplasm^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Tofersen (42 nmol; intracerebroventricular injection; single dose) sodium extends median survival of SOD1^G93A ALS mice to 143 days (pre-symptomatic) or 139 days (symptomatic) and reduces cortical and cerebellar SOD1 mRNA by 40%-60%^[2].
Tofersen (0.25 mg/kg; i.v.; single dose) sodium combined with optimized FUS and microbubbles delivers 5-10% of the administered dose to mouse brain tissue, achieving >3.5-fold higher brain uptake than without FUS^[5].
Tofersen (0.5 mg/kg; i.v.; once weekly; 9 weeks) sodium combined with FUS reduces SOD1 expression in targeted mouse brain cortex regions and preserves spinal cord motor neuron count without inducing neuroinflammation in G93A-SOD1 ALS mice^[5].
Delivery of Tofersen (ISIS 333611) sodium to the CSF of SOD1^G93A rats distributes to the brain and spinal cord, reduces spinal cord SOD1 mRNA and protein levels, and prolongs survival in this ALS model^[6].
Tofersen (Intrathecal) sodium extends survival and improves muscle response function in transgenic rodent models of SOD1-mediated ALS^[8].
Tofersen (Intrathecal) sodium lowers SOD1 protein concentrations in non-human primates^[8].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

7128 (free acid)

C₂₃₀H₂₉₈N₇₂Na₁₉O₁₂₃P₁₉S₁₅

1898254-60-8

Solid

White to light yellow

[Tofersen (sodium)]

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen, away from moisture)

• [1]. Steffke C, et al. Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1-Linked Amyotrophic Lateral Sclerosis. Ann Neurol. 2025;98(6):1318-1334.

  [2]. Weiss A, et al. RNAi-mediated silencing of SOD1 profoundly extends survival and functional outcomes in ALS mice. Mol Ther. 2025;33(8):3917-3938.

  [3]. Miller TM, et al. Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2022;387(12):1099-1110.

  [4]. Miller TM, et al. Long-Term Tofersen in SOD1 Amyotrophic Lateral Sclerosis. JAMA Neurol. 2026 Feb 1;83(2):115-125.

  [5]. Ediriweera GR, et al. Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy. J Control Release. 2025;378:221-235.

  [6]. Miller TM, et al. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. Lancet Neurol. 2013 May;12(5):435-42.

  [7]. Duan C, et al. Intrathecal administration of a novel siRNA modality extends survival and improves motor function in the SOD1G93A ALS mouse model. Mol Ther Nucleic Acids. 2024;35(1):102147. Published 2024 Feb 15.

  [8]. Miller T, et al. Phase 1-2 Trial of Antisense Oligonucleotide Tofersen for SOD1 ALS. N Engl J Med. 2020 Jul 9;383(2):109-119.  [Content Brief]

  [9]. Wiesenfarth M, et al. Effects of tofersen treatment in patients with SOD1-ALS in a "real-world" setting - a 12-month multicenter cohort study from the German early access program. EClinicalMedicine. 2024;69:102495. Published 2024 Feb 15.