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Rare Neurological Disorders Pregnancy: Not applicable in the usual adult context; if inadvertently used in pregnancy, consult specialist — no teratogenicity data

Nusinersen

Brand names: Spinraza

Adult dose

Dose: 12 mg intrathecal injection on days 0, 14, 28, and 63 (loading), then every 4 months (maintenance)
Route: Intrathecal
Frequency: 4 loading doses then every 4 months
Max: 12 mg per dose
Administer by experienced clinician via lumbar puncture. Remove CSF equal to nusinersen volume before injection. Dilute to 5 mL if needed. Pre-procedure: coagulation check, anaesthesia or sedation for children.

Paediatric dose

Dose: 12 mg per dose (flat dose) mg/kg
Route: Intrathecal
Frequency: Same loading and maintenance schedule as adults
Max: 12 mg per dose
Licensed for ALL ages including neonates — most efficacious when started pre-symptomatically (newborn screening); seek specialist paediatric neuromuscular opinion at neuromuscular centre

Dose adjustments

Renal

No dose adjustment — intrathecal drug, no systemic pharmacokinetics

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Licensed for ALL ages including neonates — most efficacious when started pre-symptomatically (newborn screening); seek specialist paediatric neuromuscular opinion at neuromuscular centre

Clinical pearls

  • Mechanism: antisense oligonucleotide (ASO) — nusinersen is a modified 18-mer ASO that hybridises to SMN2 pre-mRNA; modulates splicing of exon 7 to include it in SMN2 transcript; produces full-length functional SMN protein from SMN2 gene (compensating for SMN1 deletion/mutation in SMA)
  • ENDEAR trial (NEJM 2017): nusinersen vs sham procedure in SMA Type 1 infants — 41% achieved motor milestone response vs 0% control; significant motor function improvement; first disease-modifying therapy for SMA
  • SMA types: nusinersen licensed for all SMA types (1, 2, 3, and pre-symptomatic) — pre-symptomatic treatment (via newborn screening) gives best outcomes; babies treated before symptom onset can achieve near-normal motor development
  • MHRA 2017: first antisense oligonucleotide licensed for a neurological disease in UK; NICE TA588 recommended for Type 1 SMA; restricted to specialist neuromuscular centres
  • Alternative therapies: onasemnogene abeparvovec (Zolgensma — gene therapy, single IV dose, licensed up to 21 kg), risdiplam (Evrysdi — oral SMN2 splicing modifier); choice depends on SMA type, age, weight, cost
  • CSF SAMPLING: always remove equal volume of CSF before nusinersen injection to prevent intrathecal pressure increase; send removed CSF for analysis (biomarkers)

Contraindications

  • Coagulopathy or thrombocytopenia (lumbar puncture contraindicated)
  • Active infection at lumbar puncture site
  • Spinal abnormalities preventing lumbar access (relative — may need imaging-guided approach)

Side effects

  • Post-lumbar puncture headache (post-dural puncture headache — common)
  • Back pain
  • Thrombocytopenia (monitor platelet count)
  • Renal toxicity (monitor urine protein — antisense oligonucleotide class effect)
  • Coagulation abnormalities (aPTT prolongation)
  • CSF pleocytosis (may interfere with CSF analysis for other conditions)

Interactions

  • Anticoagulants (increased lumbar puncture bleeding risk — consider timing)
  • No pharmacokinetic drug interactions (intrathecal delivery)

Monitoring

  • Platelet count and coagulation tests (before each lumbar puncture)
  • Urine protein (renal toxicity — monthly urine dipstick or spot protein:creatinine ratio)
  • Motor function assessments (CHOP-INTEND, HFMSE scales — at specialist centre)
  • Bulbar function and respiratory status (SMA disease monitoring)

Reference: BNFc; BNF 90; ENDEAR trial NEJM 2017;377(18):1723-1732; CHERISH trial NEJM 2017;377(18):1733-1742; NICE TA588; MHRA 2017. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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