Mara Dierssen-researcher 2012

Mara Dierssen, MD, PhD

with Rafael de la Torre, Co-Investigator

Centre for Genomic Regulation, Barcelona, Spain

FRAXA Awards:
$45,000 in 2014
$45,000 in 2013
$34,000 in 2012

Drs. Dierssen and de la Torre are conducting preclinical studies in Fragile X knockout mice and a double blind, randomized clinical trial in Fragile X patients using Mega Green Tea Extract, which contains 45% by weight epigallocatechin gallate (EGCG). 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 are currently waiting to hear results from Dr. Dierssen.

Project Goal

by Mara Dierssen, MD, Ph.D., 2/1/2012

Epigallocatechin gallate as a therapeutic agent in Fragile X syndrome

Fragile X syndrome (FXS) is therapeutically still an orphan disease. We here propose that rare diseases leading to intellectual disability, such as FXS, 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.