Studies to assess the carcinogenic potential of tofersen have not been conducted.L46108
Tofersen was negative in in vitro (bacterial reverse mutation and mammalian cell chromosomal aberration) and in vivo (mouse micronucleus) assays.L46108
In a study to assess effects on fertility and reproductive function, tofersen (0, 3, 10, 30 mg/kg) was administered every other day to male and female mice prior to and during mating and continuing in females to gestation day (GD) 7. Adverse effects on male reproductive organs (seminiferous tubular degeneration, seminiferous tubule dilatation, spermatid retention, apoptosis of epithelial cells, increased cellular debris in the testes, and hypospermia in the epididymis) were observed at the highest dose tested; however, there were no adverse effects on functional endpoints. Plasma exposure at the no-effect dose (10 mg/kg) for adverse effects on male reproductive organs was approximately 2 times that in humans at the recommended human dose of 100 mg.L46108
Subcutaneous administration of tofersen (0, 3, 10, 30 mg/kg) every other day to pregnant mice during the period of organogenesis resulted in no adverse effects on embryofetal development. Plasma exposure at the highest dose tested (30 mg/kg) was approximately 4 times that in humans at the recommended human dose (RHD) of 100 mg.L46108
Subcutaneous administration of tofersen (0, 3, 10, 30 mg/kg) every other day to pregnant rabbits during the period of organogenesis resulted in no adverse effects on embryofetal development. Plasma exposure at the highest dose tested (30 mg/kg) was approximately 20 times that in humans at the RHD.L46108
Subcutaneous administration of tofersen (0, 3, 10, or 30 mg/kg) every other day to male and female mice prior to and during mating and continuing in females throughout organogenesis resulted in no adverse effects on pre- or postnatal development. Plasma exposures at the highest dose tested (30 mg/kg) were approximately 4 times that in humans at the RHD.L46108
Tofersen is under an intrathecally administered antisense oligonucleotide targeting the mutated SOD1 gene that causes amyotrophic lateral sclerosis (ALS).L46108 Although there were various causes of ALS, 2% of ALS cases are due to SOD1 mutations, with more than 200 SOD1 mutations documented.A259028,A259033 Tofersen was granted accelerated approval from the FDA on April 25, 2023, as the first treatment for adults with ALS caused by SOD1 mutation.L46133 Continual FDA approval is contingent on clinical benefits from ongoing trials, particularly the Phase 3 ATLAST study in people with presymptomatic SOD1-ALS.L46133
Tofersen demonstrated efficacy in reducing the concentration of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks, although the ALS Functional Rating Scale–Revised did not improve.A259023 However, it could potentially be due to the short timeframe of tofersen treatment, and more longterm trials are being conducted to confirm this hypothesis.A259023
Fitur visualisasi ini dikembangkan menggunakan pendekatan Graph Theory untuk memetakan hubungan polifarmasi dan molekuler. Entitas (Obat, Target, Gen) direpresentasikan sebagai Simpul (Nodes), sedangkan hubungan biologisnya sebagai Sisi (Edges).
drugbank-id dan name pada skema XML DrugBank.targets/target yang memuat polipeptida sasaran.gene-name dan varian snp-effects.Tata letak grafik menggunakan algoritma Force-Directed Graph (Barnes-Hut). Model fisika ini menerapkan gaya tolak-menolak antar simpul (Gravitasi: -3000) agar tidak tumpang tindih, serta gaya pegas (Spring: 0.04) pada garis penghubung untuk fleksibilitas interaksi.