Studies of Mega Green Tea Extract to Treat Fragile X Syndrome

With a $124,000 grant from the FRAXA Research Foundation from 2012-2014, Dr. Mara Dierssen and Dr. Rafael de la Torre conducted preclinical studies in fragile X knockout mice and a clinical trial in fragile X patients using Mega Green Tea Extract, which contains 45% by weight epigallocatechin gallate (EGCG).

Mara Dierssen, MD, PhD
$124,000 Grant
Mara Dierssen, MD, PhD
Principal Investigator
Centre for Genomic Regulation, Barcelona, Spain
2012-2014 FRAXA Research Grant
$124,000 over 3 Years

EGCG is a phytoestrogen (plant estrogen) which has weak estrogen effects. More importantly, in neurons it binds estrogen beta receptors (ERβ) and this, in turn leads to inhibition of PI3K, mTOR, and ERK1/2, all of which are known to be overactive in Fragile X. The mouse studies will help to identify biomarkers of efficacy based on the activity of these pathways.

The trial includes 40 patients, ages 18-30, and was conducted in Barcelona, Spain.

We here propose that rare diseases leading to intellectual disability, such as fragile X syndrome, where alterations in synaptic plasticity are involved, may benefit from treatments targeting Estrogen Receptors beta (ER-ß). Estrogens can act as neuroprotective agents, promoting synaptic plasticity and neurite outgrowth, and health benefits derived from flavonoids, phytoestrogens of natural origin are partially explained by their interaction with membrane ER. Selective ER-ß flavonoids are thus good candidates for their therapeutic evaluation in intellectual disabilities.

Our preliminary results suggest that the flavonol epigallocatechin gallate (EGCG), the isoflavone dadzein and the flavone apigenin could be good candidates for cognitive enhancement therapy in FXS. EGCG also targets central intracellular transduction signals (EGCG is an ATP-inhibitor of PI3K, and mTOR and ERK1/2) altered in FXS and improves memory recognition in a FXS animal model.

Rafael de la Torre

Rafael de la Torre, PhD
Co-Principal Investigator