An international team of researchers has identified a new disease: Pyrin Associated Autoinflammation with Neutrophilic Dermatosis (PAAND). This disease makes the immune system respond as if there were a bacterial skin infection. As a result, the skin starts producing a protein that causes severe skin lesions, fevers, and pain.

“Detailed work by clinicians told us that we were dealing with a genetic disease”, lead scientific researcher Adrian Liston explains. “Thanks to advances in DNA sequencing technology, we were able to sequence the genome of Belgian, English, and French patients and find the mutation causing the disease.”

The mutation was discovered in the MEFV gene. This gene was already known to cause an autoinflammatory disease called Familial Mediterranean Fever (FMF) in patients who inherited mutated copies from both their parents. FMF often skips generations, but PAAND is passed on from generation to generation, because one single copy of the mutation is enough to cause the disease. Therefore, patients’ children have a fifty-fifty chance of developing PAAND.

Therapeutic possibilities

“For almost ten years, we’ve been trying to understand this disease”, says lead clinical researcher Carine Wouters. “Our findings are the result of intense collaboration between clinicians and scientists. I’m delighted to see how it has increased our understanding of rare mutations, and how it has opened up therapeutic perspectives.”

The researchers were able to identify a potential cure: they repurposed an anti-arthritis drug targeting the protein that also causes PAAND. The treatment has already been tested in an English volunteer, with remarkable results: skin lesions cleared rapidly, and the fevers and pain disappeared. A larger-scale clinical trial that involves the Flemish patients is about to start.

“Thanks to DNA sequencing technology, this is an amazing time to be working on genetic diseases”, Professor Liston continues. “Every month we’re cracking clinical cases that were too hard to solve just a few years ago. The next challenge is making sure our healthcare system can keep pace with scientific developments. Our patients are in a difficult situation, as health insurance funds don’t always reimburse the costs of advanced diagnostic tests or new treatments. This is an opportunity for all stakeholders involved: negotiations between policy-makers, pharmaceutical industry, clinical doctors, and researchers are essential to make new therapies and existing therapies for new indications available for patients in medical need.”

Click here to read the study in Science Translational Medicine

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