A global team of researchers at the Max Planck Institute of Biochemistry has made a groundbreaking discovery that saves the lives of patients suffering from toxic epidermal necrolysis. This rare but often fatal reaction to common medications causes widespread detachment of the skin. Using innovative spatial proteomics – one of the most advanced molecular biology tools – the team identified the inflammatory JAK/STAT pathway as the main driver of disease. After validating their findings in pre-clinical models, they successfully treated the first seven patients worldwide with JAK inhibitors, all of which showed rapid and full recovery.
The researchers used spatial proteomics to analyze skin samples from patients with toxic epidermal necrolysis. This cutting-edge approach, known as Deep Visual Proteomics, merges powerful microscopy with AI-driven analysis, laser-guided microdissection and ultimately ultra-high sensitivity mass spectrometry. They zoomed in on individual cells and studied them like never before, creating a map of the thousands of proteins driving this deadly reaction.
By applying spatial proteomics to archived patient samples suffering from toxic epidermal necrolysis, we were able to precisely isolate and analyze 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, a class of drugs already used to treat other inflammatory conditions, such as atopic dermatitis or rheumatoid arthritis.”
Thierry Nordmann, first author, clinician-scientist at the Max Planck Institute of Biochemistry and senior dermatologist