Cinacalcet Rectifies Hypercalcemia in a Patient With Familial Hypocalciuric Hypercalcemia Type 2 (FHH2) Caused by a Germline Loss-of-Function Gα11 Mutation

“…The effectiveness of cinacalcet in rectifying the FHH2‐associated loss‐of‐function abnormalities caused by the downstream Gα 11 protein has been assessed by in vitro and in vivo studies. Thus, recent in vitro studies have shown that cinacalcet improves the signalling responses of HEK293 cells stably expressing the CaS receptor (HEK–CaS receptor), which have been transiently transfected with FHH2‐associated Gα 11 mutants (Babinsky et al ., ; Gorvin et al ., ). Indeed, nanomolar doses of cinacalcet were demonstrated to rectify the impaired Ca 2+ i responses associated with loss‐of‐function Gα 11 mutations (Table ) (Babinsky et al ., ; Gorvin et al ., ).…”

“…Thus, recent in vitro studies have shown that cinacalcet improves the signalling responses of HEK293 cells stably expressing the CaS receptor (HEK–CaS receptor), which have been transiently transfected with FHH2‐associated Gα 11 mutants (Babinsky et al ., ; Gorvin et al ., ). Indeed, nanomolar doses of cinacalcet were demonstrated to rectify the impaired Ca 2+ i responses associated with loss‐of‐function Gα 11 mutations (Table ) (Babinsky et al ., ; Gorvin et al ., ). Moreover, siRNA knockdown studies showed that cinacalcet enhanced the signalling mediated by the FHH2 mutant Gα 11 proteins rather than by exerting indirect effects on endogenously expressed wild‐type Gα 11 proteins (Babinsky et al ., ).…”