Photo 1: Maria Francisca Madeira, Mónica Santos and Vittoria Beruto; Photo 2: Mónica Santos, Carmen Agustín-Pavón and Enrico Tongiorgi 

Rett syndrome is a rare neurodevelopmental disorder caused by mutations in a gene (MECP2). It is a syndrome that almost exclusively affects female children who have motor alterations, respiratory dysfunction, cognitive and behavioral problems. Although under-investigated, emotional changes, such as anxiety and depression, are a very relevant component in patients with this syndrome.
The “Drug screening Pro-Rett” project aims to test a panel of drugs already approved by the FDA for various diseases other than Rett syndrome, and to understand their therapeutic potential for this syndrome. This project involves the University of Trieste (project leader), the University of Valencia and the University of Coimbra, through CNC-UC. In Trieste, Professor Enrico Tongiorgi's laboratory showed that 14 drugs (code named D1, D2, D3, etc.) could rescue the alterations observed in neurons in animal models of Rett syndrome. Given these results, the project team now aims to test the potential of some of these drugs to rescue the behavioral/emotional changes characteristic of Rett syndrome, such as anxiety, depression and cognitive problems. This is the work being carried out at CNC-UC, led by Mónica Santos (leader of the Neurobiology of Mental Diseases sub-group) and with the participation of Maria Francisca Madeira (CNC-UC PhD student in the Experimental Biology and Biomedicine Doctoral Program) and Vittoria Beruto (visiting researcher from the University of Trieste). The work carried out at CNC-UC so far indicates that the drug D5, administered in the diet of animals with the disease, both male and female, is proving effective in counteracting the symptoms of Rett syndrome. In particular, the effects of the drugs on general health and on five groups of typical Rett symptoms were measured: sensory (touch and temperature), emotional (anxiety, depression), cognitive (memory), motor and gastrointestinal. Among the results obtained so far, it was observed that after treatment for three weeks with the drug D5, the general health score of the male Rett mice did not worsen. In addition, the drug D5 also induced in the males with the disease a recovery of the normal levels of anxiety and depression-like behaviors observed in the behavioral tests. This result is significant and it is therefore believed that the drug D5 can address emotional symptoms.
The patent for these drugs, which until now was only valid in Italy, has been extended to international level for two of these drugs (D4 and D5) and to European level for one of them (D1). If their clinical therapeutic potential is confirmed, the internationalization of the patent opens the door to the potential marketing of these drugs for use in patients with Rett syndrome.
Mónica Santos explains that “If we really can prove these results, it will represent great hope for the treatment of patients with Rett syndrome, since these drugs are already on the market and therefore the time needed for their possible administration will be greatly reduced compared to the development of a new drug”. The researcher adds that "The next step is to identify the mechanism of action. That's why it's so important to continue the research and renew funding to better understand these processes and also test the D1 and D4 drugs."
This project was funded by ProRett Ricerca, started in 2024 and has now been renewed for another year.