Tofersen
Neuroprotective agents for ALS
Neuroprotective agents for ALS
Intrathecal antisense oligonucleotide for ALS caused by SOD1 mutations. It lowers SOD1 protein production; approval was based on a fall in neurofilament light.
Quick facts
- Group
- Neuroprotective agents for ALS
- Target
- SOD1 mRNA (superoxide dismutase 1)
- Used for
- Amyotrophic lateral sclerosis
- Key effects
- Pain · Fatigue · Joint and muscle pain
- Monitor
- Neurological symptoms after each dose
- ATC
- N07XX22
No doses: the clinician sets them by the current guideline.
Mechanism of action
In SOD1-ALS, mutations in the superoxide dismutase 1 gene produce a harmful protein that builds up in motor neurons. Tofersen is an antisense oligonucleotide that targets SOD1 mRNA, reducing the synthesis of SOD1 protein. Treated patients had lower plasma neurofilament light, a blood marker of axonal injury, which is reasonably likely to predict clinical benefit; confirmatory trials are ongoing.
- Injected intrathecally into the cerebrospinal fluid
- Binds SOD1 mRNA in motor neurons
- Less mutant SOD1 protein is made
- Less axonal injury: plasma neurofilament light falls
Indications
- Amyotrophic lateral sclerosis in adults with a mutation in the SOD1 gene (accelerated approval) Amyotrophic lateral sclerosis →
Adverse effects
Common
- Pain, including back pain after lumbar puncture
- Fatigue
- Joint and muscle pain
- Increased white cells in the cerebrospinal fluid
Contraindications
- Hypersensitivity to tofersen or to any component of the solution
Key interactions
- Other medicines
- No clinically important interactions are listed in the patient information; every medicine and supplement is still reviewed before each dose.
What is monitored
- Neurological symptoms after each dose (weakness, numbness, bladder or bowel changes)
- Headache and visual changes
- Signs of meningeal irritation
- Laboratory tests as scheduled by the treating team
Administration and safety
- Given intrathecally by lumbar puncture by an experienced clinician, in an office or clinic.
- Loading doses come first, then maintenance doses at regular intervals; missed doses are rescheduled promptly.
- Genetic testing confirms the SOD1 mutation before treatment.
Pregnancy and breastfeeding
Data are limited; pregnancy or breastfeeding is reported to the treating doctor.
Nursing care
- After each lumbar puncture, watch for headache, back pain and new neurological symptoms.
- Teach the patient to report weakness, numbness, bladder or bowel changes, visual changes or fever with stiff neck at once.
- Support the patient and family with the genetic implications of SOD1-ALS.
- Record function and breathing to follow the disease.
Pharmacokinetics
- Absorption
- Given intrathecally by lumbar puncture, by professionals experienced in the procedure.
Test yourself
Think of the answer, then tap the question to see it.
Which ALS patients are candidates for tofersen?
Adults with ALS associated with a mutation in the SOD1 gene.
How does tofersen act?
It is an antisense oligonucleotide that targets SOD1 mRNA and reduces the synthesis of SOD1 protein.
Which biomarker supported the accelerated approval of tofersen?
A reduction in plasma neurofilament light, a marker of axonal injury.
Connections
← Back to the class: Neuroprotective agents for ALS
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Tofersen Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2023); FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene (U.S. Food and Drug Administration, 2023); Amyotrophic lateral sclerosis: MedlinePlus Genetics (MedlinePlus Genetics (U.S. National Library of Medicine), 2016); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.