FOP is an extremely debilitating disease manifested through inflammatory-related episodes of heterotopic ossification, that is, bone formation at extra-skeletal sites. Although a number of potential therapies are under investigation at this moment, unfortunately there is no proven effective treatment yet. FOP is caused by gain-of-function mutations in the ACVR1 gene, resulting in enhanced SMAD1/5 signaling and aberrant differentiation and activation of bone cells. Preliminary results have shown that the PI3Ka inhibitor BYL719 (Alpelisib), currently under investigation for the treatment of several types of cancer, effectively inhibits heterotopic ossification in a preclinical model of FOP by interfering with ACVR1 downstream signaling. Together with Dr. Francesc Ventura (University of Barcelona, Spain), this project aims to optimize the use BYL719 as a potential therapy for FOP, and investigate the mechanisms by which BYL719 may normalize ACVR1 signaling. This information is absolutely required to implement this potential therapy for treatment of FOP patients and other forms of heterotopic ossification.
In April 2020, Dr. Sanchez-Duffhues has been awarded with €100.000 by the patient association FOP Italia (http://www.fopitalia.it), for his application entitled “PI3K inhibitors as a treatment for Fibrodysplasia ossificans progressiva (FOP)”.