Dyson 2018 MiP2018
Dyson A (2018)
A clinical need exists for novel therapies geared towards treatment of reperfusion injury, the secondary damage caused by necessary revascularisation following ischaemic events such as heart attack and stroke. Evidence suggests that downregulating oxidative metabolic activity is able to reduce the quantity of damaging reactive oxygen species generated by restoration of an adequate oxygen supply. Hydrogen sulphide (a known metabolic modulator via inhibition of mitochondrial complex IV) has shown some efficacy in animal models of ischaemia/reperfusion injury however, no sulphur-based compounds have been trialled to date in randomised phase 2/3 studies in patients. We recently reported that ammonium tetrathiomolybdate (ATTM; [NH4]2MoS4), a copper chelator long used for the treatment of Wilson’s disease and more recently as an anti-cancer agent, is a slow-release sulphide donor. We demonstrated that ATTM possesses a unique sulphide-release profile that promotes targeted cellular delivery of sulphide. It is able to safely modulate metabolism in vivo following intravenous administration to rats and, given at reperfusion, confers cardioprotection, neuroprotection and survival benefit in ischaemia/reperfusion injury models. These data have provided much encouragement for translation of this molecule to the clinical setting as a novel adjunct therapy for reperfusion injury. The preclinical development of ATTM for this purpose is ongoing.
Labels: MiParea: Pharmacology;toxicology
Stress:Ischemia-reperfusion Organism: Rat
Univ College London, UK. - [email protected]