Media release

From: WEHI

World-first cure for lethal skin disease achieved in landmark study

A team of researchers has for the first time cured patients with a lethal skin disease, in a breakthrough study that could lead to an approved curative therapy for the deadly condition.

Toxic epidermal necrolysis (TEN) is a rare but potentially fatal disease with limited treatment options.

Now a pioneering study involving a critical collaboration with WEHI has identified a new driver of the disease that can be targeted with an existing class of drugs, marking the first ever cure for the life-threatening condition.

At a glance

• Researchers have cured a group of patients diagnosed with a lethal skin disease, in a landmark study published in Nature.
• Toxic epidermal necrolysis (TEN) is a rare but deadly condition that currently has limited treatment options and no approved cure.
• WEHI researchers played a significant role in achieving the unprecedented results after uncovering a new driver of disease that can be therapeutically targeted with an existing class of drugs.

Toxic epidermal necrolysis is a life-threatening condition that causes widespread blistering and detachment of the skin, often requiring hospitalisation.

The rare condition is triggered by an extremely severe adverse reaction to common medications, such as allopurinol (used to treat gout) and certain over the counter antibiotics.

With a mortality rate of around 30%, the disease can rapidly progress from a seemingly harmless rash into a life-threatening condition.

Second author and WEHI molecular biologist Dr Holly Anderton said the team used JAK inhibitors – a class of drugs currently approved for the treatment of inflammatory diseases like rheumatoid arthritis – to treat patients with the disease.

“Finding a cure for lethal diseases like this is the holy grail of medical research. I am beyond proud of this incredible research collaboration that has already helped to save the lives of multiple patients,” Dr Anderton said.

“All seven people treated with this therapy in our study experienced rapid improvement and a full recovery, in staggering results that has likely unlocked a cure for the condition.”

By the time patients present to hospital with TEN, their symptoms are already at a critical stage, requiring similar treatment to burns victims, including intensive care and life support.

“It can take a patient weeks to recover from the damage, even after they’ve stopped taking the medication that triggered the adverse reaction,” Dr Anderton said.

“Being able to rapidly halt progression of this disease, as we have seen in our study, will make a huge difference to the standard of care for patients diagnosed with this life-threatening condition.”

Pioneering collaboration In a collaboration with the Max Planck Institute of Biochemistry (Germany), researchers used spatial proteomics to analyse skin samples from patients with TEN.

Using this cutting-edge approach, known as Deep Visual Proteomics, the team was able to zoom in on individual cells and study them in unprecedented detail, creating a map of the thousands of proteins that drive this deadly disease.

Dr Thierry Nordmann, first author and clinician scientist at the Max Planck Institute of Biochemistry said: “By applying spatial proteomics to archived patient samples suffering from toxic epidermal necrolysis, we were able to precisely isolate and analyse individual cell types and understand what is actually occurring in the skin of these patients. “We identified a striking hyperactivation of the inflammatory JAK/STAT pathway, revealing an opportunity to intervene in this deadly condition with JAK inhibitors.”

This theory was tested across multiple preclinical studies, including in a unique disease-approximating mouse model developed by Dr Anderton and colleagues at WEHI.

The overwhelmingly positive results from these studies allowed researchers to proceed directly to trialling the treatment in TEN patients.

This research led to the groundbreaking result of seven patients in Germany being cured of the life-threatening disease.

Researchers hope the milestone findings will soon pave the way for a clinical trial aimed at the regulatory approval of JAK inhibitors as a cure for TEN.

The study, “Spatial proteomics identifies JAKi as treatment of a lethal skin disease”, is published in Nature (DOI: 10.1038/s41586-024-08061-0).