NEJM:Tofersen疗-SOD1-AS

The antisense oligonucleotide drug Tofersen mediates the degradation of the superoxide dismutase 1 (SOD1) messenger RNA degradation, reducing SOD1 protein synthesisThe intrauterine drug Tofersen can be used to treat amyotrophic lateral sclerosis (ALS) caused by THE SOD1 mutationresearchers recently conducted a Phase 1-2 incremental dose trial to assess the safety and efficacy of tofersen in ALS patients with SOD1 mutationsThe study was divided into 20, 40, 60 or 100 mg dose groups, and participants were randomly given 5 doses of tofersen or placebo for 12 weeksThe main results of the study were safety and pharmacokineticsThe secondary result is an 85th day change in the concentration of cerebrospinal fluid (CSF) SOD150 participants, and in most of the participants, adverse events associated with lumbar punctures were observedFour and five participants who received tofersen treatment, respectively, showed cerebrospinal fluid white blood cell count and increased proteinOf the participants treated with tofersen, one died of pulmonary embolism on the 137th day and the other from respiratory failure on the 152st day, and one participant in the placebo group died of respiratory failure on the 52rd dayOn the 85th day, the cSF SOD1 concentration in the Tofersen group and the placebo group changed to the baseline: 2 percent for the 20 mg dose group, -25 percent for the 40 mg dose group, -19 percent for the 60 mg dose group, and -33 percent for the 100 mg dose groupin adults with ALS caused by the SOD1 mutation, receiving intra-tofersen injections reduces the concentration of spinal fluid SOD1, with some patients experiencing cerebrospinal fluid and cell growth, and most patients observing adverse events associated with lumbar punctures