The Italian Medicines Agency – AIFA, after receiving the favourable opinion of the national ethics committee for paediatric studies, has given the green light to the first global clinical trial of the drug Mirtazapine for Rett Syndrome, named MirtaRett.

The trial, coordinated by the University of Trieste, will take place in leading Italian hospitals specialising in the treatment of Rett Syndrome patients and is entirely funded by non-profit grants, in particular by the non-profit project “Angelini for future” by Angelini Pharma SpA, together with Fondazione Canali Onlus, Ico Falck Onlus, and Amedei e Setti Onlus. The trial management is handled by the Consorzio per Valutazioni Biologiche e Farmacologiche (CVBF), a non-profit organisation providing clinical research services in Italy.

The actual start of the trial will take about 2 months, during which UniTS, as the coordinating centre, together with the four clinical centres in Milan, Genoa, Siena and Messina, will organise the recruitment and treatment of patients.

The trial is exclusively for female patients, as Rett Syndrome is a genetic condition affecting 1 in 10,000 girls and is the second leading cause of intellectual disability in females (Petriti et al. Systematic Reviews (2023) https://doi.org/10.1186/s13643-023-02169).

The trial will involve a total of 54 patients aged between 5 and 40, divided into three age groups of 18 participants each (5–10, 11–17 and 18–40 years).

Rett Syndrome is a deceptive genetic disorder caused by random, unpredictable mutations in the MECP2 gene in the reproductive cells (sperm or eggs) of otherwise healthy parents. It manifests in the second year of life, when girls begin to speak and walk, leading to rapid regression of speech and loss of purposeful hand use. In the following years, girls develop seizures and breathing difficulties, which are the main cause of death, although many patients can reach adulthood, albeit with severe physical and mental impairments.

Gene restoration experiments in animal models have shown that the disease can be completely reversible, but no definitive cure currently exists.

The project began in 2009, thanks to funding from Telethon, Fondazione San Paolo, Fondazione Casali, Beneficentia Stiftung, and the parent associations AIRETT Onlus and ProRett Ricerca Onlus. Over 15 years of research conducted in the laboratory directed by Prof. Enrico Tongiorgi at the Department of Life Sciences, University of Trieste, numerous experimental findings have demonstrated the efficacy of Mirtazapine in alleviating certain symptoms. Additional evidence in support of the drug came from a retrospective study with the Rett Reference Centre at Le Scotte Hospital in Siena, where the drug was administered as standard care for anxiety, repetitive behaviours, and sleep disturbances over a period of 1 to 5 years in 40 adult Rett patients. Beyond the expected benefits on anxiety and sleep, the study also