Cysteine-lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose-finding study.

ABSTRACT:

Aim

To investigate whether mesna-sodium-2-mercaptoethane sulfonate) can reduce diet-induced fat gain in mice, and to assess the safety of single ascending mesna doses in humans to find the dose associated with lowering of plasma tCys by at least 30%.

Methods

C3H/HeH mice were shifted to a high-fat diet ± mesna in drinking water; body composition was measured at weeks 0, 2 and 4. In an open, phase I, single ascending dose study, oral mesna (400, 800, 1200, 1600 mg) was administered to 17 men with overweight or obesity. Mesna and tCys concentrations were measured repeatedly for a duration of 48 hours postdosing in plasma, as well as in 24-hour urine.

Results

Compared with controls, mesna-treated mice had lower tCys and lower estimated mean fat mass gain from baseline (w

SUBMITTER: Vinknes KJ 

PROVIDER: S-EPMC11497255 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature