Sepsis is a life-threatening organ dysfunction by the  overreaction of the immune system to an infection, affects more than 1.5 million people and kills at least 270,000 every year in the U.S. alone. The standard treatment of antibiotics and fluids is not effective for many patients, and those who survive face a higher risk of death.

What happens in a septic status? 

First, an infection begins in the body. The immune system responds by creating drastic inflammation that impairs blood flow and forms blood clots, which can cause tissue death and trigger a chain reaction leading to organ failure. Afterward, the body overcorrects itself by suppressing the immune system, which in turn increases infection susceptibility. 

In new research, the lab of Shaoqin “Sarah” Gong, a professor with the Wisconsin Institute for Discovery at the University of Wisconsin-Madison, reported a new nanoparticle-based treatment that delivers anti-inflammatory molecules and antibiotics.

The new nanoparticles delivered the chemical NAD+ or its reduced form NAD(H), a molecule that has an essential role in the biological processes that generate energy, preserve genetic material and help cells adapt to and overcome stress. While NAD(H) is well known for its anti-inflammatory function, clinical application has been hindered because NAD(H) cannot be taken up by cells directly.

What are the results of this study? 

They used mouse models for the experiment. Gong’s lab tested the NAD(H)-loaded nanoparticles (lipid-coated calcium phosphate or metal-organic) in multiple mouse models including multidrug-resistant pathogen-induced polymicrobial bacteremia, as well as a puncture-induced sepsis model with secondary infection by a common illness-causing bacteria called P. aeruginosa. 

For instance, in an endotoxemia mouse model, mice without any treatment or treated with free NAD(H) died within two days. In contrast, mice treated with NAD(H)-loaded nanoparticles all survived. These animal studies demonstrated that the NAD(H) nanoparticles can help maintain a healthy immune system, support blood vessel function and prevent multiorgan injury.

This new technology can lead to the development of new therapies for sepsis and could apply to many inflammatory conditions such as autoimmune diseases or any inflammation scenarios. More studies are needed with large animals to establish a safe dose and pathway to start people trials. 

SOURCE:

Mingzhou Ye, Yi Zhao, Yuyuan Wang, Ruosen Xie, Yao Tong, John-Demian Sauer, Shaoqin Gong (jUNE 6, 2022). NAD(H)-loaded nanoparticles for efficient sepsis therapy via modulating immune and vascular homeostasis. Nature Nanotechnology. Retrieved from :https://www.nature.com/articles/s41565-022-01137-w

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