A Novel Therapy/Companion Diagnostic (BAM15 And mtDNA) for Sepsis and Sepsis-induced Acute Kidney Injury

This technology includes a therapy and companion diagnostic which can be used for the early diagnosis and treatment of sepsis and sepsis-induced acute kidney injury (AKI). Mitochondrial damage plays a key role in sepsis-induced acute kidney injury BAM15 [2-ftuorophenyl){6-[(2- fluorophenyl)am ino]{1 ,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine] is a mitochondrial uncoupler that protects mitochondria with more specificity and less cytotoxicity than other uncouplers. Mitochondrial DNA (mtDNA) is a damage associated molecular pattern that is increased in human sepsis. Using a mouse model of sepsis, we showed that BAM15 improved survival and reduced kidney injury, and also reduced circulating and urinary mtDNA. Scientifically, this suggests that BAM15 reduces mitochondrial injury and/or improves recovery from damage. More critically, BAM15 and mtDNA form a drug-companion biomarker pair for sepsis/sepsis AKI that would allow selection of patients for therapy, enhance drug dose finding, and create a novel surrogate biomarker for drug effect.