Drug candidate found to prevent lethal lung inflammation

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They find a potential treatment to prevent serious inflammatory diseases, such as pulmonary inflammation associated with COVID or sepsis, since it reduces the damage caused by the overactivation of neutrophils in the immune system.

Our body has soldiers ready to go into battle against the pathogens that attack us. Specifically, neutrophils – the most abundant type of white blood cell – are the body’s first line of defense against infection. Pathogens can activate neutrophils, which have various ways of protecting us. The problem arises if these immune cells become overactive, because in that case they can damage the body’s own tissues.

This is one of the problems that some patients infected with the coronavirus have experienced, because the tissue of the lungs is full of blood vessels and this makes them very prone to neutrophil attacks and severe acute lung injuries can trigger the syndrome. acute respiratory distress (ARDS), the leading cause of death from COVID-19.

Researchers have found a drug candidate capable of preventing lethal lung inflammation in mice by inhibiting a protein called PTP1B. This finding may contribute to the development of better treatments against serious inflammatory pathologies such as sepsis and COVID-19. The results of the work have been published in JCI Insight.

Nicholas Tonks, Caryl Boies Professor of Cancer Research at Cold Spring Harbor Laboratory (CSHL), and leader of the research said: “When you think of COVID-19, acute lung injury and ARDS underlie the fatal aspects of COVID-19. illness”. “So when the pandemic took hold, we were wondering if there was anything we could do to help, to understand this aspect of the disease and suggest ways to treat it.”

PTP1B inhibitor reduced lung tissue damage

Tonks graduate student Dongyan Song studied whether using a PTP1B inhibitor drug candidate could counteract the deadly consequences of hyperactive neutrophils in mice, and found that pre-treating mice with the PTP1B inhibitor decreased damage to the lung tissue. The trial results showed that without the treatment, less than half of the mice survived acute lung injury and ARDS, whereas when they received pretreatment, all survived.

Without PTP1B inhibitor treatment, less than half of the mice survived acute lung injury and ARDS, whereas when pretreated, all survived

The researchers took advantage of a natural process called neutrophil aging, which the body uses to control the lifespan of immune cells. Neutrophils become less dangerous as they age, and the researchers found that inhibiting PTP1B accelerates neutrophil aging. “An aging neutrophil is like a soldier without weapons,” Song explained, adding: “So no matter how many neutrophils flood an area, they won’t be able to do serious damage.”

Tonks and Song are now working to better understand how PTP1B inhibitors affect the immune system. Tonks hopes her research will help create new treatments and preventative therapies for various inflammatory diseases. His laboratory is currently collaborating with DepYmed, Inc. to bring PTP1B inhibitor drug candidates to clinical trials. Their goal is to develop small-molecule drug candidates that target the PTP family of proteins, which may lead to new therapeutic options for the treatment of human diseases, such as cancer and metabolic and neurodegenerative diseases.

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