Repurposing of Acid Ceramidase to Protect Against Hepatic Ischemia/Reperfusion Injury

Mount Sinai Health System Background
Hepatic ischemia-reperfusion (IR) injury is a common pathological process that occurs in various clinical settings such as liver resection, transplantation, hemorrhagic shock, and other surgical procedures. It is characterized by first the interruption, and then re-establishment, of the liver blood flow and oxygen supply. Restoration of blood supply should protect the liver from injury, however, paradoxically such reperfusion following ischemia often leads to further hepatocyte death and tissue damage. Currently there is no accepted method of preventing IR injury to the liver or other organs during surgery.
Over two decades of research has documented that the sphingolipid, ceramide, is a key bioactive signaling molecule that mediates the proliferation, survival and death of cells. Ceramide accumulates in response to diverse cellular stresses (e.g., inflammation, oxidative stress, apoptosis, infection and others) and contributes to the pathology of many diseases (e.g., diabetes, cardiovascular disease, Alzheimer’s disease, IR injury).
A growing body of evidence has shown that the accumulation of ceramide occurs in multiple models of ischemia and reperfusion injury. These and other findings suggest that ceramide is central to the pathogenesis of IR-induced liver injury and that the modulation of ceramide levels may be a therapeutic strategy to prevent or treat IR injury in diverse clinical settings.
Technology Overview
Researchers at the Icahn School of Medicine at Mount Sinai have shown that using the ceramide hydrolase, acid ceramidase (AC) on liver IR injury in mice, is effective in protecting the liver against toxicity due to IR.
Stage of Development
In vivo data in IR injury mouse model shows effectiveness of acid ceramidase in protecting the liver.
Benefits

No other method is available to protect against IR injury

Applications

Effective prophylactically against IR injury during transplant or other forms of surgery

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