GMR24T1137

Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder that causes accelerated aging in children. Currently, no cure is available for this disorder and ongoing clinical trials do not revert the disease. Mutations causing HGPS syndrome fall on lamin A/C gene and generate a truncated form, the progerin, that, acting as a dominant negative, affects lamin A/C nuclear organization. The nuclear lamina is important for controlling the DNA three-dimensional structure, a key player in the regulation of genome functionality. In 2020 the first treatment of progeria with lonafarnib drug was approved in USA. Other drugs are in preclinical tests as progerinin. However, to date no studies were done on the role of lonafarnib or progerinin on the DNA conformation. In this project, we will use advanced experimental techniques, including methods that we developed in our laboratory, in the mouse model of HGPS, to identify chromatin structure alterations resistant to pharmacological treatments.