Researchers used JAK inhibitors to treat toxic epidermal necrolysis, a disease emerging as a major public health issue.
Researchers have published results of a world-first study that could lead to an approved curative therapy for toxic epidermal necrolysis.
They say this is the first time ever that patients have been cured of the fatal skin disease, for which there are currently limited treatment options.
Their research has been published in the journal Nature.
The study, a collaboration between researchers at the University of Melbourne’s WEHI and the Max Planck Institute of Biochemistry in Germany, identified a new driver of the disease that could be targeted with an existing class of drugs.
Toxic epidermal necrolysis 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,” she 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 usually 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,” said Dr Anderton.
“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.”
As part of their study, the researchers used spatial proteomics to analyse skin samples from patients with TEN. Using an 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 the disease.
Dr Thierry Nordmann, first author and clinician scientist at the Max Planck Institute of Biochemistry said that by applying spatial proteomics to archived patient samples suffering from toxic epidermal necrolysis, they 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,” he said.
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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 led to the groundbreaking result of seven patients in Germany being cured of the life-threatening disease.
The 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.
Nature 2024, online 16 October
