Researchers found new treatment for pneumonia

Inflammatory diseases such as COPD and blood poisoning are increasingly threatening public health.

Often, these conditions are the result of an overactive immune system.

Therefore, the discovery of the molecule wakes up TH5487 to stir. The molecule has the ability to disarm the protein, which plays an important role in inflammatory diseases.

The molecule has been shown to exacerbate pneumonia in mice.

The discovery was carried out by scientists at the Karolinska Institute in Stockholm, at the University of Stockholm, at the University of Texas, as well as at NTNU and Sintef in Trondheim.

Start button for excessive response

Inflammation is the reaction of your immune system, which aims to limit injury or infection. But for some, inflammation can be harmful:

For those with a lot of inflammatory diseases, the body produces a lot of ROS signals. It is an abbreviation for "reactive oxygen species" and suggests inflammation and damage to the cell's heritage, DNA.

Then the enzyme OGG1 comes to the pitch. An enzyme is an active protein that promotes reactions in our body.

OGG1's mission is to eliminate damaged DNA in our cells. This repair turns out to be a kind of start button for the immune response in our body.

This is a start button that strengthens the immune system for people with autoimmune diseases. These are diseases in which the immune system begins to attack healthy cells.

The repair enzyme makes the inflammation stronger.

Earlier studies have shown that mice lacking OGG1 can not trigger a strong immune response and, as a result, become milder inflammation than normal mice.

Five years ago, when working at the Karolinska Institute (KI), the Sintef researcher Torkild Visnets was interested in this enzyme.

He and colleagues will develop a substance that could delay the restoration of enzymes.

It is not clear that the DNA damage that the enzyme is about to repair is so problematic:

– In the past, we thought that ROS accidentally damaged the DNA. But now it seems that these changes, in general, can be harmed, but on the other hand, part of the normal immune response, explains Visne. But this is something we need to explore more.

Think of an enzyme

In 2013, the research team began to hunt down the possibility of making the OGG1 enzyme less active.

"Our idea was to search for a chemical that would attract protein repair. This drug is used to" disarm "the protein by translating it: indicate the protein that has already found the damaged DNA, thereby pushing it out. In other words, the protein is deprived of the opportunity to start excessive immune response.

"I've worked a lot in measuring activities with this type of enzyme in the past, but with very laborious methods," says Visne.

– But by developing a method that allowed us to read the activity of enzymes with fluorescence, ie, restoring the DNA light color, we were able to read thousands of samples in just a few hours.

After examining the potency of the substance that could capture the enzyme by 18,000, the researchers went back to the drug that was able to disable OGG1. It was a year passed.

Further development of the molecule in the laboratory

Subsequently, the labor-intensive process began to improve the fabric so that it had all the necessary qualities for working in a living cell.

For two years, researchers made about a thousand small variations of the substance. Finally they went with the new and promising TH5487 who simply got their name because it came after the drug that was done earlier and called TH5486.

The drug had three main characteristics sought by researchers:

1. It was on the inflammatory protein OGG1 so that it became absorbed and could not bind to DNA.

2. It can also deactivate OGG1 in cells that were alive

3. In animals, it was very stable.

Fresher Mouse in Texas

The breakthrough occurred when researchers from the University of Texas tested this substance in mice with severe lung inflammation.

TH5487 can quickly and effectively eliminate the work of repairing enzymes. Thus, the immune cells could not detect the appearance of inflammation and abstain from the lungs.

Therefore, pneumonia became much more sensational. Therefore, the research team believes that they have found a new type of inflammation that can be used instead of existing treatments or in addition.

"The goal is to create a medicine that can work with people. The road is tall, the rules are complicated and the costs are high. But we have the belief that we have discovered a piece that can be very important in the treatment of all autoimmune diseases to blood poisoning case, "says Visne.

reference:

All, T. et al .: OGG1 small molecule inhibitor inhibits the expression and inflammation of inflammation genes. Science (2018) (summary) DOI: 10.1126 / science.aar8048