A pediatric quantitative systems pharmacology model of neurofilament trafficking in spinal muscular atrophy treated with the antisense oligonucleotide nusinersen.

ABSTRACT: Phosphorylated neurofilament heavy subunit (pNfH) has been recently identified as a promising biomarker of disease onset and treatment efficacy in spinal muscular atrophy (SMA). This study introduces a quantitative systems pharmacology model representing the SMA pediatric scenario in the age range of 0-20 years with and without treatment with the antisense oligonucleotide nusinersen. Physiological changes typical of the pediatric age and the contribution of SMA and its treatment to the peripheral pNfH levels were included in the model by extending the equations of a previously developed mathematical model describing the neurofilament trafficking in healthy adults. All model parameters were estimated by fitting data from clinical trials that enrolled SMA patients treated with nusinersen. Th

SUBMITTER: Paris A 

PROVIDER: S-EPMC9931427 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature