Target Health Blog

CHAPLE Disease and Possible Treatment With a Repurposed Drug

November 6, 2017

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Gastroenterology
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CHAPLE disease is also known as CD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy. The disease is a form of primary intestinal lymphangiectasia (PIL), or Waldmann's disease, and was first described in 1961 by Thomas A. Waldmann, M.D., an NIH Distinguished Investigator at the National Cancer Institute, at NIH. Children with the condition can experience severe gastrointestinal distress and deep vein blood clots. No effective treatments are available to ameliorate or prevent these life-threatening symptoms. Now, 56 years later, a genetic cause and potential treatment strategy for a CHAPLE disease has been identified.

In a study published in the New England Journal of Medicine (2017; 377:52-6), genes were analyzed from 11 children with CHAPLE disease and their families. Results showed that each child had two copies of a defective CD55 gene that prevented them from producing a cell surface protein of the same name. The CD55 protein helps regulate the immune system by blocking the activity of complement, a group of immune system proteins that can fight infections by punching holes in the cell membranes of bacteria and other infectious agents. However, complement also can damage the body's tissues. The study found that in CHAPLE disease, uninhibited complement resulting from a lack of CD55 protein damaged blood and lymph vessels along the lower digestive tract, leading to the loss of protective immune proteins and blood cells. In many patients, this process caused a range of symptoms, such as abdominal pain, bloody diarrhea, vomiting, problems absorbing nutrients, slow growth, swelling in the legs, recurrent lung infections, and blood clots. 

After discovering that complement hyperactivity was driving these severe symptoms, the authors tested drugs already approved by the U.S. Food and Drug Administration for the treatment of other diseases to see if they block this process in samples of patient immune cells. The authors found that complement production decreased when cells were exposed to eculizumab, a therapeutic antibody approved to treat another rare condition called paroxysmal nocturnal hemoglobinuria. The NIAID team and their collaborators plan to study eculizumab in people with CHAPLE disease with the hope that the therapeutic could become the first effective treatment for the disorder.

CAPTION: This light microscope image shows the gut tissue of a child with CHAPLE disease. The large white areas in the bottom right corner are enlarged lymphatic vessels, which can contribute to intestinal distress.

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