Generic Name

Spinraza

Mechanism

Spinraza is a *single-stranded antisense oligonucleotide (ASO)* that targets a splice site within intron 7 of the *SMN2* pre‑mRNA. The ASO binds to the SMN2 transcript, enhancing exon 7 inclusion during splicing. This leads to production of a full‑length, functional SMN protein that compensates for the loss of SMN1 in patients with spinal muscular atrophy (SMA).
• Key points:
• Increases SMN2‑derived SMN protein levels by ~30‑40 %.
• Improves motor neuron viability and reduces motoneuron loss.
• Delivered intrathecally to bypass the blood‑brain barrier and achieve CNS exposure.

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Pharmacokinetics

• Administration: Intrathecal injection into the cerebrospinal fluid (CSF).
• Distribution: Widely distributed in the CSF and lumbar spinal cord; high affinity uptake by spinal motor neurons.
• Half‑life: ~40 hours in CSF; terminal half‑life ~150 hours; steady state achieved after 3–4 months.
• Metabolism: No significant hepatic metabolism; degraded by 3′‑exonucleases.
• Excretion: Renally via the kidneys; minimal accumulation after repeated dosing.

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Indications

• Spinal Muscular Atrophy (SMA) – All types (1, 2, and 3) in patients of any age, whether pre‑symptomatic or symptomatic.
• Early‑onset SMA (type 1) – Improves survival and motor milestones when started within the first 6 months of life.
• Established disease – Provides neuroprotection, slows disease progression, and may improve respiratory function.

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Contraindications

• Contraindicated in patients with hypersensitivity to any component of the formulation.
• Caution
• Severe systemic illness, including uncontrolled infections or sepsis.
• Patients requiring spinal instrumentation or other neurosurgical procedures that may compromise CSF access.
• Pregnancy / lactation: no safety data; use only if benefits outweigh potential risks.
• Warnings
• Respiratory depression / apnea, particularly in infantile patients.
• Potential for urinary tract infections (UTIs) after lumbar puncture.
• Possible allergic contact dermatitis at injection site.

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Dosing

• Loading dose:
• 12 mg intrathecal (IVT) at weeks 0, 2, and 6 (infant) or at month 0, 2, and 4 (child/adult).
• Maintenance dose:
• 8 mg intrathecal every 4 weeks thereafter (infant) or monthly (child/adult).
• Administration details
• Administered via a lumbar puncture performed by an experienced spinal specialist.
• Use of small‑gauge needles, aseptic technique, and patient monitoring to reduce complications.

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Adverse Effects

• Pre‑treatment: Monitor for respiratory status; maintain hydration; assess for underlying infection.
• Post‑treatment: Observe for signs of infection, neurologic decline, or UTI symptoms.

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Monitoring

• Motor function
• HINE‑1 or CHOP‑Intensive Care Unit (ICU) scores for infants/children.
• 6‑MWT or NSAA in older children/adults.
• Respiratory
• Pulmonary function tests (FVC, peak cough flow).
• Oxygen saturation and sleep studies if clinically indicated.
• Laboratory
• CBC with differential (neutropenia risk).
• Serum electrolytes, kidney and liver panels, especially in renal or hepatic impairment.
• CSF
• Monitor for neuroinflammation or infection post‑lumbar puncture.
• Infants
• Growth parameters (weight, head circumference).
• Feeding tolerance and apnea episodes.

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Clinical Pearls

1. Start Early – The greatest benefit of Spinraza is achieved when treatment begins before extensive motor neuron loss; ideally within the first 6 months of life.
2. Combination Therapies – For children/adults transitioning to gene therapy (Onasemnogene abeparvovec‑vzi), maintain Spinraza for 6–12 months post‑infusion to bridge disease progression.
3. Injection Site Care – Use a 25‑G needle, perform the procedure in a sterile environment, and apply topical antibiotic ointment to reduce UTI risk.
4. Respiratory Protection – Early placement of a non‑invasive ventilation mask or tracheostomy may be warranted for type 1 SMA; Spinraza can slow decline but not reverse established respiratory failure.
5. Drug Interactions – No clinically significant interactions; however, concomitant use of neuro‑toxic agents may mask motor improvement.
6. Long‑Term Safety – While long‑term data (> 3 years) continue to accrue, most studies show no new safety signals; routine monitoring remains essential.

Spinraza has now revolutionized SMA care, offering a disease‑modifying approach that improves survival, motor milestones, and quality of life when integrated into multidisciplinary SMA management plans.