Targeting the neuronal calcium sensor 1 for treating wolfram syndrome

Abstract

The present invention relates to novel therapeutic ways for treating Wolfram Syndrome (WS) by targeting the neuronal calcium sensor 1 (NCS1). The present inventors have demonstrated that WFS1, which loss of function is responsible of the Wolfram Syndrome, forms a complex with the neuronal calcium sensor 1 (NCS1). The inventors have further demonstrated that WFS1 associates with NCS1 to prevent its degradation by the proteasome and that NCS1 regulates VDAC expression and mitochondrial respiratory chain. Thus, present invention provides an agonist of NCS1 for use in the treatment of WS. Such an agonist is e.g. a NCS1-encoding polynucleotide, an inhibitor of the proteasome or of calpains. The inventors have further shown that overexpression of NCS1 in WS cells allows increasing complex II driven respiration. The present invention further relates to a method for predicting the severity of WS by measuring the NCS1 level in a sample obtained from a patient.

Dependencies are inferred from the claim text.