Monograph- Selecting disease-modifying medications in 5q spinal muscular atrophy-Article text

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Spinal muscular atrophy (SMA) is an inherited lower motor neuron disease caused by alterations in the survival motor neuron 1 gene (SMN1). Three medications have been recently approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec-xioi, and risdiplam. Nusinersen is an intrathecal antisense oligonucleotide that alters SMN2 pre-mRNA. Onasemnogene abeparvovec-xioi is an intravenous SMN1 gene replacement therapy, and risdiplam is an oral small molecule splicing modifier of SMN2. No head-to-head studies have been conducted comparing these medications, so selecting the appropriate treatment can be challenging.<br /><br />When selecting a therapy for an individual with SMA, several factors should be considered, including the age of the individual, comorbidities such as liver or kidney disease, and the efficacy and safety profiles of the medications. Early initiation of treatment is critical for obtaining the best outcomes.<br /><br />The efficacy of the medications has been assessed using different scales depending on the age and motor function of the individual. These scales include the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), Hammersmith Infant Neurological Examination section 2 (HINE-2), Bayley Scales of Infant and Toddler Development third edition (BSID-III), Hammersmith Functional Motor Scale—Expanded (HFMSE), Revised Upper Limb Module (RULM), and 32-item Motor Function Measure Scale (MFM-32).<br /><br />Safety considerations for each medication include potential side effects such as thrombocytopenia, renal toxicity, liver injury, and thrombotic microangiopathy. Monitoring platelet count, coagulation studies, and urine protein levels is recommended for nusinersen, while laboratory monitoring for liver injury and thrombocytopenia is recommended for onasemnogene abeparvovec-xioi. No standard laboratory monitoring is required for risdiplam.<br /><br />The choice of medication depends on individual patient characteristics and contraindications. Treatment algorithms can help guide the decision-making process. The future of SMA treatment may include expanded age indications, different delivery mechanisms, combination treatments, and the development of new SMA-specific medications.<br /><br />In conclusion, treatment selection for individuals with SMA involves considering various factors such as age, comorbidities, safety profiles, and efficacy. Early initiation of treatment is crucial for optimal outcomes.

Keywords

Spinal muscular atrophy

lower motor neuron disease

SMN1

nusinersen

gene replacement therapy

risdiplam

efficacy

safety profiles

treatment selection

optimal outcomes

SMA