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This cholesterol metabolism gene is upregulated in sepsis patients with poor prognoses, and its inhibition shows promise as an effective treatment. Sepsis is the body’s extreme immune response to an existing infection, giving rise to an enhanced chain reaction throughout the body. This can lead to organ failure and potentially death. It is the costliest reason for hospital admission worldwide. Sepsis results in early death, occurring within the first 14 days of diagnosis, and the development of chronic critical illness (CCI). Patients with chronic critical illness (CCI) frequently develop persistent inflammation, immunosuppression, and catabolism syndrome (PICS), characterized by impaired physical function and an over 40% one-year mortality rate. Survivors of sepsis experience reduced quality of life, physical dysfunction, and less long-term survival.
Lipids and lipoproteins, such as high-density lipoprotein (HDL) and low-density lipoprotein (LDL), play a protective role in sepsis through antioxidant and anti-inflammatory activities and clearance of bacterial toxins. However, lipid metabolism becomes dysregulated in sepsis, leading to HDL conversion into a dysfunctional and pro-inflammatory HDL and organ failure progression. Although some studies have investigated the genetic foundations of lipid metabolism in sepsis, there is still a need for further identifying potential targets for the effective treatment of sepsis.
Researchers at the University of Florida, University of Michigan, and UCLA identified a gene involved in cholesterol metabolism, which is overexpressed in sepsis patients, leading to very poor clinical outcomes. In preclinical studies, pharmacological blockage of the cholesterol metabolism gene results in complete rescue from death, acting as an effective sepsis treatment.
Pharmacologic blockade of a cholesterol metabolism gene for effectively treating sepsis
University of Florida, University of Michigan, and UCLA researchers identified a cholesterol metabolism gene, which is overexpressed in sepsis patients, resulting in poor clinical outcomes like CCI and early death. The researchers have demonstrated that pharmacological blockade, using a pre-clinical sepsis model, results in complete rescue from death, thus acting as an effective sepsis treatment.
