Nusinersen
Spinal muscular atrophy (SMA) therapies
Spinal muscular atrophy (SMA) therapies
Antisense oligonucleotide injected by lumbar puncture for spinal muscular atrophy. It makes SMN2 produce more full-length SMN protein.
Quick facts
- Group
- Spinal muscular atrophy (SMA) therapies
- Target
- SMN2 pre-mRNA (intronic splicing silencer ISS-N1 in intron 7)
- Used for
- Spinal muscular atrophy in infants
- Key effects
- Headache · Respiratory infections · Constipation
- Monitor
- Growth in infants
- ATC
- M09AX07
No doses: the clinician sets them by the current guideline.
Mechanism of action
Nusinersen is an 18-base 2′-O-methoxyethyl phosphorothioate antisense oligonucleotide. Injected into the cerebrospinal fluid, it is taken up by motor neurons and pairs by Watson–Crick base pairing with ISS-N1, an intronic splicing silencer just after exon 7 of the SMN2 pre-mRNA. This blocks the hnRNP repressor proteins, exon 7 is kept in the mature mRNA, and more full-length, functional SMN protein is made.
- Injected intrathecally into the cerebrospinal fluid
- Pairs with the ISS-N1 silencer in SMN2 intron 7
- hnRNP repressors cannot bind: exon 7 is included
- More full-length SMN protein: motor neurons survive
Indications
- Spinal muscular atrophy in infants, children and adults Spinal muscular atrophy →
Adverse effects
Common
- Headache, back pain and vomiting related to lumbar puncture
- Respiratory infections: runny nose, sore throat, cough
- Constipation
- Fever and falls
Contraindications
- Hypersensitivity to nusinersen 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
- Blood and urine tests before starting and before each dose, looking for bleeding problems and kidney damage
- Growth in infants
- Motor function scales to judge response
Administration and safety
- Given intrathecally by a doctor experienced in lumbar puncture, in an office or clinic.
- Loading doses come first, then maintenance doses at regular intervals; missed doses are rescheduled promptly.
Pregnancy and breastfeeding
Data are limited; pregnancy or breastfeeding is reported to the treating doctor.
Nursing care
- Before each dose, check that the blood and urine results have been reviewed.
- After the lumbar puncture, watch for headache, back pain and vomiting.
- Teach carers to report bleeding, bruising, changes in urine or swelling.
- Track the child's weight and length on growth charts.
Pharmacokinetics
- Absorption
- Given intrathecally by lumbar puncture because it does not cross the blood–brain barrier well.
- Distribution
- Taken up by neurons and glial cells throughout the spinal cord and brain; the part that reaches the blood binds plasma proteins.
Test yourself
Think of the answer, then tap the question to see it.
What sequence does nusinersen bind?
The ISS-N1 intronic splicing silencer just downstream of exon 7 in SMN2 pre-mRNA.
What is the result of nusinersen binding?
Exon 7 is included in SMN2 mRNA, so more full-length SMN protein is made.
By what route is nusinersen given, and why?
Intrathecally by lumbar puncture, because the oligonucleotide does not cross the blood–brain barrier well.
Which laboratory problems are checked before each nusinersen dose?
Bleeding problems and kidney damage, with blood and urine tests.
Connections
← Back to the class: Spinal muscular atrophy (SMA) therapies
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Nusinersen Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2018); Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy (Yonsei Medical Journal, via PubMed Central, 2020); SMN2 gene: MedlinePlus Genetics (MedlinePlus Genetics (U.S. National Library of Medicine), 2018); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.