How a Melbourne team helped solve the mystery of a deadly skin disease

A medicine, often harmless, such as aspirin, causes a sudden and suppressive immune response. Immune cells in the skin, eyes, and throat begin to release toxic proteins; The outer layer of skin begins to die and peel off.

About a third of people with TEN die, and many who survive are left with injuries for life.

There are no risk factors. Scientists do not understand the mechanism, and there are no effective treatments. “We really don’t understand it at all,” Anderton said.

Enter spatial proteomics

Proteins are the building blocks of life. Every cell in our body contains a network of forges that forge them whenever the cell needs to do something: eat, divide, attack, die.

Study proteins and you will understand what the cell is trying to do.. But the average human cell produces more than 10,000 proteins, and each cell is different.

Great new advances in microscopes, lasers and artificial intelligence are opening up this world to science.

Researchers in Germany applied these techniques, spatial proteomics, to a group of seven patients with TEN; One man’s case was so severe that doctors considered death likely.

Using a laser scalpel, they cut out individual cells. The artificial intelligence model then separated the immune cells from the skin cells.

A mass spectrometer that measures the mass and charge of protein building blocks then identified thousands of proteins in diseased cells.

It immediately became clear that the diseased cells were producing high levels of interferons, a protein used to kill viruses.

This suggested a new treatment that no one had previously thought of: JAK inhibitors, which reduce the effect of interferon.

But you can’t just give a new therapy to a patient, even one who is likely to die, without some testing. Anderton enters. She developed a mouse model of TEN as part of a separate study on wound healing.

A letter came from Germany out of the blue: could you test this drug? Anderton jumped at the chance.

To carry out the experiments, it took her several months of work in the laboratory on animals. Anderton remembers coming in one day to find that TEN mouse lesions had stopped growing. It was a “wow” moment.

“I remember looking at those mice and thinking, ‘This could really stop this.’

She wrote an email to the German team. They started JAK therapy almost immediately.

All seven patients treated have recovered.

Currently, the institute has created its own spatial proteomics system. “This is a really big leap,” said Dr. Maria Tanzer, one of Anderton’s co-authors and a colleague at the Walter and Eliza Hall Institute.

Obvious targets were diseases in which differences in cells matter, such as cancer, in which different parts of the same tumor can behave differently, says Arutha Kulasinghe, founding scientific director of the Queensland Center for Spatial Biology.

Anderton never met the person whose life she could save.

“They’re on the other side of the world,” she says. “But I still feel that special connection.”

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