Senior Researcher
Department of Neuroscience
Istituto Superiore di Sanità
Viale Regina Elena, 299
00161 Rome
Italy
T: +390649902037
Ε: [email protected]
The aim of the research group working at the Istituto Superiore di Sanità in Rome is to understand the dysfunctional molecular mechanisms causing MLC disease. MLC is mainly due to mutations in MLC1, a protein highly expressed in the brain by a population of cells called astrocytes. These cells play a primary role in coordinating the balance of ions and water in the brain. Mutations in the MLC1 protein affect the ability of astrocytes to regulate these processes, leading to macrocephaly, cysts, and myelin vacuolation. By studying mouse astrocytes and a human astrocytoma cell line, Dr. Ambrosini discovered specific molecular alterations in the MLC disease process. To gain a deeper knowledge of MLC defective mechanisms in a more relevant patient-based experimental model, they recently generated human astrocytes from MLC patient skin fibroblasts by induced pluripotent stem cell (iPSC) reprogramming/differentiation. Astrocytes derived from patient iPSC represent a powerful tool to explore disease mechanisms and screen potential drugs in a patient-tailored way. In these cells, they have confirmed and extended the knowledge of MLC molecular defects. The goal is now to identify molecular targets (e.g. genes, proteins) that can be treated with drugs and other pharmacological compounds to rescue the MLC specific cellular defects, thereby providing evidence for the potential of a drug-based therapy to treat MLC. The clinical and phenotypic improvement observed over time in some patients has revealed that the pathological process is partially reversible and that correction of MLC dysfunctional molecular pathways may be a promising strategy to slow down disease progression.