Nusinersen

Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder. Nusinersen, marketed as Spinraza, is a medication used in treating spinal muscular atrophy (SMA), a rare neuromuscular disorder. In December 2016, it became the first approved drug used in treating this disorder. Nusinersen cost US$750,000 in the first year and US$375,000 annually after that in the United States as of 2019. Nusinersen has orphan drug designation in the United States and the European Union. The drug is used to treat spinal muscular atrophy associated with a mutation in the SMN1 gene. It is administered directly to the central nervous system (CNS) using intrathecal injection. In clinical trials, the drug halted the disease progression. In around 60% of infants affected by type 1 spinal muscular atrophy, the drug also significantly improved motor function. Although not observed in the trial patients, a reduction in platelets as well as a risk of kidney damage are theoretical risks for antisense drugs and therefore platelets and kidney function should be monitored during treatment. In summer 2018, several cases of communicating hydrocephalus in children and adults treated with nusinersen emerged; it remains unclear whether this was drug related. Spinal muscular atrophy is caused by loss-of-function mutations in the SMN1 gene which codes for survival motor neuron (SMN) protein. People survive owing to low amounts of the SMN protein produced from the SMN2 gene. Nusinersen modulates alternate splicing of the SMN2 gene, functionally converting it into SMN1 gene, thus increasing the level of SMN protein in the CNS. The drug distributes to CNS and to peripheral tissues. The half-life is estimated to be 135 to 177 days in CSF and 63 to 87 days in blood plasma. The drug is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis and does not interact with CYP450 enzymes. The primary route of elimination is likely by urinary excretion for nusinersen and its metabolites.