Data de publicació electrònica: 25-03-2019

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.

This work was supported by the Spanish Ministry of Economy and Competitiveness; ‘Centro de Excelencia Severo Ochoa 2013-2017’; the ‘Centres de Recerca de Catalunya’ Programme / Generalitat de Catalunya’; the Centro de Investigación Biomédica en Red Enfermedades Raras (CIBER) of Rare Diseases; DIUE de la Generalitat de Catalunya [Grups consolidats SGR 2014/1125]; Ministerio de Economía, Industria y Competitividad de España MINECO [SAF2013-49129-C2-1-R and SAF2016-79956-R].