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A phase 1, randomized double-blind, placebo controlled trial to evaluate safety and efficacy of epigallocatechin-3-gallate and cognitive training in adults with Fragile X syndrome

2019; Elsevier BV; Volume: 39; Issue: 2 Linguagem: Inglês

10.1016/j.clnu.2019.02.028

1532-1983

Rafael de la Torre, Susana Solá, Magı́ Farré, Laura Xicota, Aida Cuenca‐Royo, Joan Rodríguez, Alba León, Klaus Langohr, María Gomis-González, Gimena Hernández, Susanna Esteba, Laura del Hoyo Soriano, Júdit Sánchez-Gutiérrez, María José Cortés, Andrés Ozaita, Josep M. Espadaler, Ramón Novell, Rafael Martínez‐Leal, Montserrat Milà, Mara Dierssen, Aida Cuenca‐Royo, Alessandro Príncipe, Gimena Hernández, Gonzalo Solís Sánchez, Joan Rodríguez, Josep M. Espadaler, Júdit Sánchez-Gutiérrez, Klaus Langohr, L.U. Tomas Roca, Laura del Hoyo Soriano, Laura Xicota, Magı́ Farré, Mara Dierssen, Rafasel de la Torre, Montserrat Fitó, Susana Solá, Alba León, O.C. Banea, Ramón Novell, Susanna Esteba, Rafael Martínez‐Leal, María José Cortés, Montserrat Milà, Rafaël Maldonado, Arnau Busquets‐Garcia, Andrés Ozaita, María Gomis-González,

Cognitive Functions and Memory

Background & aims Despite the wide spectrum of experimental compounds tested in clinical trials, there is still no proven pharmacological treatment available for Fragile-X syndrome (FXS), since several targeted clinical trials with high expectations of success have failed to demonstrate significant improvements. Here we tested epigallocatechin-3-gallate (EGCG) as a treatment option for ameliorating core cognitive and behavioral features in FXS. Methods We conducted preclinical studies in Fmr1 knockout mice (Fmr1−/y) using novel object-recognition memory paradigm upon acute EGCG (10 mg/kg) administration. Furthermore we conducted a double-blind placebo-controlled phase I clinical trial (TESXF; NCT01855971). Twenty-seven subjects with FXS (18–55 years) were administered of EGCG (5–7 mg/kg/day) combined with cognitive training (CT) during 3 months with 3 months of follow-up after treatment discontinuation. Results Preclinical studies showed an improvement in memory using the Novel Object Recognition paradigm. We found that FXS patients receiving EGCG + CT significantly improved cognition (visual episodic memory) and functional competence (ABAS II-Home Living skills) in everyday life compared to subjects receiving Placebo + CT. Conclusions Phase 2 clinical trials in larger groups of subjects are necessary to establish the therapeutic potential of EGCG for the improvement of cognition and daily life competences in FXS.