Researchers identify pathway responsible for calciphylaxis, a rare and serious condition

“Our discovery has found a possible treatment that could specifically target and help patients with this disease”

(Boston)—The global burden of chronic kidney disease (CKD) is rising, with more than 800 million people affected worldwide. Vascular diseases in patients with CKD are unique and grouped as uremic vascular diseases. One of them, calciphylaxis, typically affects patients with end-stage, advanced kidney disease. It is a condition characterized by severe, painful and non-healing skin ulcers with no known cure.

 

For the first time, researchers from Boston University Chobanian & Avedisian School of Medicine in collaboration with the Massachusetts General Hospital, have discovered a novel biological pathway, called the IL6 pathway, central to the skin lesion initiation and progression. Blocking this pathway they believe, will likely prevent progression of the skin ulcers and resolve the pain seen in patients with calciphylaxis.

 

“This study reveals the presence of a pathological and harmful cycle between the fat under the skin, sweat glands and small blood vessels that keep feeding onto itself. If this cycle isn’t stopped and remains unchecked, it will lead to the skin ulcers that won’t heal. Using the specific pathway we identified, we could break this cycle and prevent the skin ulcers from getting worse,” explained corresponding author Vipul Chitalia, MD, PhD, professor of medicine. 

 

In the study, human calciphylaxis skin and blood samples were examined for proteins and genes to analyze alterations in disease-causing mechanisms. An FDA-approved drug was then applied to see if the disease-causing pathway could be suppressed.

 

According to the researchers, drugs that can block this pathway are already available, safe to use and approved for other indications. “Those drugs are likely to prevent progression of the skin ulcers and resolve the pain that we see in patients with calciphylaxis. Human trials are now needed to show the benefit of those drugs.” explained co-author Jean Francis, MD, associate professor of medicine. 

 

These findings appear online in the journal Science Translational Medicine.

 

The Partners Calciphylaxis Biorepository and Patient Registry was funded by the American Heart Association’s National Center for Research Program Winter 2015, Fellow-to-Faculty Transition Award (15FTF25980003, S.N.) and the KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award, S.N.) from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100, S.N.). This project was partially funded by the Thrombosis and Hemostasis ARC and the Center of Cross Organ Vascular Pathology (DOM, BUMC, V.C.C), AHA Cardio-oncology SFRN grant 857078 (V.C.C), R01HL166608 V.C.C, R01HL159620 V.C.C, and ASN faculty development award (S.U.N), Multidisciplinary Training Program in Cardiovascular Fellowship T32HL125232 (S.L.), AHA Career Development Award 850917 (W.Y.).

 

Note to editors:

S.U.N is a consultant for Epizon Pharma, Inozyme Pharma, Laboratoris Sanifit, Rectify Pharma, Alexion, and Fresenius Medical Therapies group, grant support by Inozyme Pharma, Laboratoris Sanifit, and Hope Pharma, and royalties from UpToDate. The other authors declare that they have no competing interests.

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