A new RNA-based therapy for the Fragile X Syndrome

The Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and autism, caused by the absence of the Fragile X Mental Retardation Protein (FMRP). Several clinical trials aiming at developing therapeutic strategies for FXS have failed to improve FXS deficits. Thus, no cure is available for FXS. Recently, promising studies investigated messenger ribonucleic acids (mRNA)-based therapy for the treatment of a broad range of diseases. mRNA play a crucial role in the cell, transferring the genetic information from the DNA into the protein, the functional product of a gene. mRNA therapy allows patients’ cells to synthetize the protein lacking in the disease, in order to cure specific conditions. One of the main biotech companies that pioneered this strategy is ModernaTX Inc. Moderna has successfully developed a technology platform to engineer synthetic mRNAs and has different clinical trials underway across several therapeutic areas. With this project, we will test mRNA-based therapy as a new approach to ameliorate FXS-related phenotypes. Specifically, we will deliver FMR1-mRNA in rodent and human neuronal and non-neuronal cells. Furthermore, we will administer FMR1-mRNA directly into the brain of the FXS mouse model in order to investigate potential benefits of the FMR1-mRNA delivery. Finally, in a translational perspective, we will explore intranasal delivery as a safe and non-invasive approach to vehicle FMR1-mRNA into the brain. The promising data obtained in our laboratory assure the feasibility of the project supporting our hypothesis of mRNA-based therapy as an innovative therapeutic approach for FXS.