Project Supported by Public Organizations in Other Countries, 2019 - 2024
CHAPLE syndrome is a newly discovered genetic disorder characterized by excessive loss of proteins in the gastrointestinal tract, referred to as protein-losing enteropathy. The disease typically presents in early childhood with facial and extremity edema in relation to hypoalbuminemia, chronic diarrhea, failure to thrive and, in extreme cases, severe thromboembolic disease that can lead to premature death. Until recently, there has been no curative therapy for CHAPLE patients. The Parties have shown that the disease is caused by loss of a complement regulatory protein due to deleterious mutations in the CD55 gene, which results in excessive activation of the complement system. Based on these scientific observations, the Parties were able to develop a targeted therapy for this deadly disease using an antibody called eculizumab, which blocks the complement protein C5. The current study aims to further dissect the molecular alterations underlying CHAPLE and CHAPLE-like diseases, identify key molecules that lead to protein-losing enteropathy and discover biomarkers that can guide therapy. The Parties anticipate that the current studies will improve the diagnosis and treatment of these disorders.