ERK Archives • Fragile X Research - FRAXA Research Foundation

Brain Organoids and Therapeutic Development for Fragile X and Other Rare Diseases

FRAXA Research Foundation June 9, 2020April 15, 2021autism, EEG, ERK, FDA

This is the first in a series of webinars focused on current topics in Fragile X research. Alysson Muotri, PhD, Professor, University of California San Diego Stem Cell Program, and Fabio C. Tucci, PhD, Chief Operating Officer and co-founder, Epigen Biosciences, will present.

Clinical Trial of Metformin for Fragile X Syndrome

FRAXA Research Foundation 2018 Grants • 2019 Grants • 2020 Grants • Clinical • Clinical Trials • Current Research Grants • Lepage, Jean-Francois • Pending Results • University of Sherbrooke, Canada May 24, 2019February 9, 2021EEG, ERK, matrix metalloproteinase, metformin, MMP9

Metformin is commonly prescribed to control high blood sugar in type 2 diabetes. With a $50,000 grant from FRAXA Research Foundation, Dr. Artuela Çaku and Dr. Francois LePage are conducting an open-label clinical trial of metformin for children and adults with Fragile X syndrome, at the University of Sherbrooke in Canada.

In Their Own Words: Reports From the International Fragile X Workshop

FRAXA Research Foundation Cogram, Patricia • Contractor, Anis • Events Recap • Kooy, Frank • Lee, Jeannie • McGill University • Moine, Herve • Razak, Khaleel • Research Updates • Smith, Carolyn B. • Sonenberg, Nahum • Todd, Peter • Vanderklish, Peter October 29, 2017December 26, 2019amygdala, autism, bumetanide, DgkK, drug repurposing, drug tolerance, EEG, ERK, FDA, Fragile X Meeting, GABA, ganaxolone, glutamate, hyperexcitability, hypersensitivity, metformin, mGluR5, minocycline, mRNAs, NIH, Rett syndrome, seizure, sleep, sound

The 18th International Fragile X and Related Neurodevelopmental Disorders Workshop in Quebec, Canada, was a great success, featuring Fragile X much more heavily than any previous meeting in this series! We asked our speakers to summarize their work in their own words, with brief updates from researchers investigating Fragile X.

18th International Fragile X and Related Neurodevelopmental Disorders Workshop, Quebec, Canada

Altered Neural Excitability and Chronic Anxiety in a Mouse Model of Fragile X

FRAXA Research Foundation 2001-2005 Grants • 2006-2010 Grants • 2016 Grants • Completed Research Grants • Disease Mechanisms • Scripps Research Institute • Treatment Targets • Vanderklish, Peter September 13, 2017January 16, 2019AMPK, ERK, GSK3

With a $35,000 grant from FRAXA Research Foundation in 2016, Dr. Peter Vanderklish at Scripps Research Institute, and colleagues, explored the basis of anxiety in Fragile X syndrome.

Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome

Theodore Coutilish 2016 Grants • 2017 Grants • 2018 Grants • Barnes, Stephanie • Completed Research Grants • Osterweil, Emily • Research Updates • Treatment Targets • University of Edinburgh, Scotland August 15, 2016March 26, 2019ERK, glutamate, lovastatin, mGluR, NMDA, seizure

FRAXA Research Foundation funded a 2016-2017 Fellowship for Dr. Stephanie Barnes in the University of Edinburgh lab of Dr. Emily Osterweil. With this $90,000 award, the team is investigating NMDA signaling in fragile X syndrome mice.

Fruit Flies to Model and Test Fragile X Treatments

FRAXA Research Foundation 2001-2005 Grants • 2006-2010 Grants • 2012 Grants • 2013 Grants • 2014 Grants • 2015 Grants • Choi, Catherine • Drug Repurposing • Jongens, Tom • McBride, Sean • Pepper, Anita • Research Grant Results • Treatment Targets • University of Pennsylvania September 13, 2015May 18, 2020ERK, FDA, fruit fly, glutamate, lithium, metformin, mGluR, mTOR, NIH

Dr. Jongens and his collaborators have found an insulin-like protein in the fly brain that is overexpressed in the Fragile X mutant fly, leading to increased activity of the insulin signaling pathway. Furthermore, they found that certain behavioral patterns in the Fragile X flies can be rescued by expressing the FX gene just in insulin producing neurons in the fly brain. In the mutant, there are other changes in the signaling pathways, including a decrease in cAMP and elevation in PI3K, mTOR, Akt and ERK activity. They now propose to study 2 medicines used for diabetes: pioglitazone (increases cAMP and decreases Akt and ERK) and metformin (inhibits mTOR), in flies and mice to validate the potential efficacy of these novel therapeutics for Fragile X.

Dr. Tom Jongens and Dr. Sean McBride study Fragile X Fruit Flies

Phase 1 Clinical Trial of Mega Green Tea Extract in Fragile X Syndrome

FRAXA Research Foundation 2012 Grants • 2013 Grants • 2014 Grants • Biomarkers • Centre for Genomic Regulation • Clinical • Clinical Trials • de la Torre, Rafael • Dierssen, Mara • Has Results • Research Grant Results September 13, 2014March 9, 2020ERK, estrogen, mTOR

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).

Social Behavior as an Outcome Measure for Fragile X Clinical Trials

FRAXA Research Foundation 2012 Grants • 2013 Grants • Clinical • Drug Repurposing • Erasmus University Rotterdam • FRAXA Research Grants • Research Grant Results • Treatment Targets • Willemsen, Rob September 13, 2013February 17, 2021AFQ056, AMPA, AMPAkines, autism, baclofen, ERK, mGluR5, minocycline, NMDA, Novartis

One of the features of the Fragile X mouse model which is relevant to the human Fragile X syndrome (and autism) is social behavior. Several tests show consistent social behavioral abnormalities in the Fragile X mouse model. With a $140,000 grant from FRAXA Research Foundation in 2012-2013, Dr. Willemsen at Erasmus University used social behavior tests to measure the effectiveness of several drug strategies.

Lovastatin Discovery in Fragile X Mice Leads FRAXA to Fund Clinical Trials

FRAXA Research Foundation Bear, Mark • Massachusetts Institute of Technology (MIT) • Osterweil, Emily • Research Updates • Treatment Targets June 11, 2013December 13, 2019autism, ERK, Fragile X Meeting, glutamate, lovastatin, mGluR, minocycline

Dr. Emily Osterweil was awarded the FRAXA Pioneer Award at the opening dinner of the 2011 FRAXA Investigators Meeting in Southbridge, MA for her work demonstrating that Lovastatin could treat Fragile X. Dr. Osterweil conducted her experiments in the MIT laboratory of Dr. Mark Bear and has since established her own laboratory at the University of Edinburgh. The team discovered that lovastatin, a drug widely prescribed for high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent epileptogenesis. The work is published in the prestigious neuroscience journal Neuron: Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome.

What Works, and What Doesn’t

Michael Tranfaglia, MD Research Updates September 7, 2012December 13, 2019Alzheimer's, AMPAkines, autism, BK channel, cancer, ERK, GABA, GSK3, lithium, mGluR5, minocycline

At the start, it’s always hard to know what methods will work best for something as complex as the development of disease-modifying treatments for Fragile X. But, we’ve always tried to let the science lead us down the right path. At this point, the results are unequivocal, and they have shaped how we are looking for the Next Great Thing in Fragile X treatments.