TREATMENT AND DIAGNOSIS OF HEREDITARY XEROCYTOSIS

摘要

The present invention relates to the treatment and the diagnosis of the hereditary xerocytosis (HX). The inventors showed that in case of HX due to mutations in PIEZO1, KCNN4 activation is responsible for erythrocyte dehydration, and that said dehydration is reversed by the inhibition of the Gardos channel (KCNN4 protein). Thus the invention relates to an inhibitor of the Gardos channel for use in the treatment of HX in a subject which is the carrier of at least one mutation of the PIEZO1 gene. Particularly, the inventors demonstrated that Senicapoc is efficient to prevent dehydration of patient erythrocytes with PIEZO mutation. They also identified that mutations V598M or F681S of the PIEZO1 channel lead to a gain of function of the channel and participate in HX physiopathology. Thus the present invention also relates to an in vitro method of diagnosing HX, comprising the detection in a biological sample of the presence of any one of these mutations.