[Combination of modifying therapies in type 2 spinal muscular atrophy]

Spinal Muscular Atrophy (SMA) is an autosomal recessive neuromuscular disorder showing peripheral hypotonia, atrophy, and weakness in the extremities and bulbar muscles. It is caused by the homozygous deletion of the SMN1 gene on chromosome 5q13. Before 2016, there was no treatment to modify the disease, and in that year it was approved nusinersen, the first drug available to treat this disease, whose action mechanism consists in regulating the SMN2 gene to increase the survival motor neuron (SMN) levels. More recently, the gene therapy onasemnogene aberparvovec-xioi (OAX) was approved for patients under two years of age. The human SMN1 gene is delivered intravenously through an adeno-associated viral type 9 vector. Both therapies appear to show significant improvement in motor function without the presence of severe adverse effects. However, it is unclear whether both treatments can be used together.

A 24-month-old male patient with a diagnosis of SMA at 18 months of age. First, he was treated with intrathecal nusinersen administration and later with OAX. When assessing the CHOP INTEND and HFSME function scales, the patient showed an increase in the performance of his motor functions.

OAX and nusinersen could be considered in sequence therapies in the presence of SMA. However, this therapy is not yet well established and has not been studied in the long term.