Cysteine‐lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose‐finding study
Authors' conclusion
Mesna reduces diet-induced fat gain in mice. In men with overweight, single oral doses of mesna (800-1600 mg) were well tolerated and lowered plasma tCys efficiently. The effect of sustained tCys-lowering by repeated mesna administration on weight loss in humans deserves investigation.
Study context
- Population
- C3H/HeH mice on high-fat diet; men with overweight or obesity
- Participants
- 17 men
- Comparison
- Mesna vs control; ascending oral mesna doses
- Mesna 400–1600 mg (humans)n = 17
- Outcome
- Mesna dose lowering plasma tCys by at least 30%
Methodological detailsdose-finding
- Dose-finding
Main finding
As reported in the abstract
Plasma tCys lowering by ≥30% · nadir (4h post-dosing)
- Mesna doses of 800 mg or higher decreased plasma tCys by 30% or more at nadir
Further findings
| Outcome | Mesna (mice) | Controls (mice) | P value |
|---|---|---|---|
| Estimated mean fat mass gain from baseline (mice) · week 2Mesna (mice) vs Controls (mice) | mean 4.54 ± 0.40 g | mean 6.52 ± 0.36 g | Poverall = .002 |
| Estimated mean fat mass gain from baseline (mice) · week 4 | mean 6.95 ± 0.35 g | mean 8.19 ± 0.34 g |
Lean mass gain and tCys (mice)
- Mesna-treated mice had lower tCys and similar lean mass gain vs controls
tCys AUC0-12h and urine tCys excretion by dose (humans)
- tCys AUC0-12h decreased with increasing dose
- P for trend < 0.001
- Urine tCys excretion increased with increasing dose
- P for trend = 0.004
- Mesna 400-1600 mg showed dose linearity
Safety
Tolerability (humans)
- Mesna doses of 400-1600 mg were well tolerated
Original publication
Cysteine‐lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose‐finding study. Diabetes Obes Metab. Published 12 July 2023. doi:10.
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