Elevated homocysteine is negatively correlated with plasma cystathionine β-synthase activity in givosiran-treated patients.

ABSTRACT: Givosiran is a subcutaneously administered, liver-targeted RNA interference (RNAi) therapeutic that has been approved for treating acute hepatic porphyria (AHP). Elevation in plasma homocysteine (hyperhomocysteinemia) has been reported in AHP patients, and treatment with givosiran has been reported to further increase homocysteine levels in some patients. The mechanism of homocysteine elevation during givosiran treatment is unknown, but has been hypothesized to be mediated by a reduction in activity of cystathionine β-synthase (CBS), which uses homocysteine as a substrate. A liquid chromatography-tandem mass spectrometry-based assay was adapted to measure circulating CBS activity. Using plasma collected from the Phase III ENVISION study, CBS activity was measured to directly evaluate wheth

SUBMITTER: Keibler MA 

PROVIDER: S-EPMC11224493 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature