Grant: Project Grant

Neurofibromatosis type 1 (NF1) is an orphan disease causing significant morbidity and mortality. It is a multisystemic genetic disorder especially characterized by cutaneous manifestations that include the development of multiple benign skin tumors, called neurofibromas. While the majority of these aesthetically disfiguring tumors are not malignant, management options are limited and the need for multiple clinical interventions contributes to significant disability and reduction of life expectancy in NF patients. No curative and nonsurgical treatment for NF exists at this time. To date, the pathogenic mechanisms associated with neurofibromas formation are still largely unknown and the clinical manifestations are highly variable, with significant differences sometimes seen within the same family. The development of neurofibromas and its severity (numbers, location) are also impossible to predict. The goal of this exiting project is to study NF1 through personalized tissue-engineered in vitro skin (TES) models to better understand disease heterogeneity and the role of dermal fibroblasts in the establishment of microenvironment favouring NF1-associated skin tumor formation/progression. The personalized 3D NF1-derived TES, i.e. directly derived from individual patient, could than be used as a preclinical model to better understand disease pathogenesis and for therapeutic testing. This innovative project will stimulate translational research in NF1 and accelerate the development of precision/personalized medicine strategies in NF, as well as to have short to mid-term impact on neurofibromatosis research and/or patient care.