Defining the Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists

Defining the Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists

With $217,500 in grants from FRAXA Research Foundation, Dr. Karen O’Malley and team studied the function of mGluR5 when it is inside cells. Many of the symptoms of Fragile X Syndrome (FXS) are thought to arise due to overactive metabotropic glutamate receptor 5 (mGluR5) signaling, which is normally opposed by the protein missing in FXS, Fragile X Protein (FMRP).

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Investigating Gene Reactivation to Treat Fragile X Syndrome

Investigating Gene Reactivation to Treat Fragile X Syndrome

With a $180,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Jeannie Lee and her team at Harvard are working to reactivate the gene that is silenced in Fragile X syndrome.

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Mechanisms of Tolerance to Chronic mGluR5 Inhibition

Mechanisms of Tolerance to Chronic mGluR5 Inhibition

Over the past few years, both Novartis and Roche sponsored large-scale clinical trials of metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) to treat Fragile X syndrome (FXS). With a $90,000 grant from FRAXA Research Foundation in 2015-2017, Dr. Mark Bear’s team will explore if mGlu5 NAMs dosed chronically causes tolerance, and if so, how it develops and to probe new avenues to prevent or circumvent it.

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Prefrontal Cortex Network Dynamics in Fragile X Syndrome

Prefrontal Cortex Network Dynamics in Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Daniel Johnston and Dr. Jenni Siegel at the University of Texas at Austin are analyzing pre-frontal cortex (PFC) dysfunction in the Fragile X model. They have preliminary evidence that Fragile X mice are severely impaired in a prefrontal cortex (PFC)-dependent task.

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Can NKCC1 Inhibitors Correct Synaptic and Circuit Hyperexcitability in Fragile X Syndrome?

Can NKCC1 Inhibitors Correct Synaptic and Circuit Hyperexcitability in Fragile X Syndrome?

With $258,000 in grants since 2013 from FRAXA Research Foundation, Dr. Anis Contractor and Dr. Qionger He at Northwestern University are exploring the potential of the available drug bumetanide to correct altered GABA signalling in a mouse model of Fragile X syndrome.

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

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

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.

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Development of a High-Content Synapse Assay to Screen Therapeutics for Fragile X Syndrome

Development of a High-Content Synapse Assay to Screen Therapeutics for Fragile X Syndrome

With a $45,000 grant from FRAXA Research Foundation in 2009, Dr. Mark Bear and Dr. Asha Bhakar used High Content Screening (HCS) to develop an assay sensitive to the effect of the FXS genotype. This project was funded in full by NIH after the first year.

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Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation funded during 2014-2015, Dr. Frank Kooy and colleagues at the University of Antwerp are conducting a double blind crossover trial of ganaxolone in patients with Fragile X syndrome. Results of this study were mixed (see Marinus: Results from Phase 2 Exploratory Clinical Study Support Continued Development of Ganaxolone in Fragile X Syndrome.

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Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

FRAXA Research Foundation awarded $122,000 over 2016-2018 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.

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Which is the right FMRP for Therapeutic Development of Fragile X Syndrome?

Which is the right FMRP for Therapeutic Development of Fragile X Syndrome?

With a 2-year, $90,000 grant from FRAXA Research Foundation over 2016-17, Dr. Samie Jaffrey at Weill Medical College of Cornell University explored which FMRP isoform is the best target to treat Fragile X syndrome.

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Biomarker Discovery and Validation for Fragile X Syndrome

Biomarker Discovery and Validation for Fragile X Syndrome

With a $60,000 grant from FRAXA Research Foundation in 2015 that was renewed in 2016, Dr. Eric Klann of New York University will research biomarkers in fraile X syndrome and how to translate these markers from mouse models to human patients.

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A Kinase Assay as a Biomarker for Fragile X Syndrome

A Kinase Assay as a Biomarker for Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation over 2017-2018, Dr. Frank Kooy at the University of Antwerp, Belgium, is investigating whether phosphorylation abnormalities are a suitable biomarker for the Fragile X syndrome. $90,000 Grant Drs. Anke Van Dijck (FRAXA fellow, ganaxolone clinical trial), Ilse van der Werf, Geert Vandeweyer, Elisa Cappuyns (FRAXA fellow, this study), Frank Kooy R. Frank Kooy, PhD Principal Investigator University of Antwerp 2018 FRAXA Research Grant $90,000 over 2 Years “This Is Your Brain on Drugs” was a large-scale US anti-drugs TV campaign promoted by Partnership for a Drug-Free America in 1987. The purpose was to discourage use of illegal drugs by showing an egg frying in a pan simulating what drugs can due to your brain. It was incredibly simple and effective. TV Guide named it one of the top 100 commercials of all time. University of Antwerp researcher Frank Kooy, PhD, has a completely different updateRead more

Function of FMRP and Test of a Novel Therapeutic Approach in a Fragile X Mouse Model

Function of FMRP and Test of a Novel Therapeutic Approach in a Fragile X Mouse Model

With a 2015-2016 $90,000 grant from FRAXA Research Foundation, Dr. Herve Moine and Dr. Andrea Geoffroy aim to uncover the exact role of FMRP and to test a novel possible means to correct for FMRP absence in the mouse model of Fragile X syndrome.

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Correcting Defects in Astrocyte Signaling in Fragile X Syndrome

Correcting Defects in Astrocyte Signaling in Fragile X Syndrome

With a $90,000 grant from the FRAXA Research Foundation from 2015-2016, Dr. Laurie Doering and Dr. Angela Scott at McMasters University studied astrocytes in Fragile X. Astrocytes, brain cells which support neurons, do not transmit signals. Several treatment strategies for Fragile X have been proposed based on correction of “astrocyte phenotypes”.

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Sensory Hypersensibility in Fragile X Syndrome and BK Channel Openers

Sensory Hypersensibility in Fragile X Syndrome and BK Channel Openers

With $366,100 in grants from FRAXA Research Foundation, these investigators at the University of Orleans studied sensory abnormalities in Fragile X mice and test the ability of a class of drugs, BK channel openers, to rescue these abnormalities.

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Fragile X Mutant Mouse Facility

Fragile X Mutant Mouse Facility

With $375,000 in grants from the FRAXA Research Foundation since 2009, Dr. David Nelson has developed an impressive array of advanced mouse models of Fragile X, at Baylor College of Medicine. These models are available to investigators worldwide on request. This resource has been essential for a broad, rapid distribution of Fragile X and related gene mouse models and has increased the pace of Fragile X research.

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MicroRNAs as Biomarkers in Fragile X Syndrome

MicroRNAs as Biomarkers in Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation in 2015-2016, Dr. Mollie Meffert and Dr. Christina Timmerman at Johns Hopkins University studied groups of small RNAs, known as microRNAs, which are greatly decreased in brain tissue of Fragile X mice vs. normal controls.

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Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome

Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome

With a $90,000 grant from the FRAXA Research Foundation, Dr. Lynne Maquat and Dr. Tatsuaki Kurosaki will investigate nonsense-mediated mRNA decay (NMD) in Fragile X. NMD is a “housekeeping” process that cells use to prevent faulty proteins from being made. But there is too much of it in Fragile X syndrome. There are already available drugs that suppress NMD – including caffeine.

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Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target

Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target

With a $90,000 grant from FRAXA Research Foundation in 2016, Dr. Carolyn B. Smith and Dr. Rache Sare at the National Institute of Mental Health investigated the basis of sleep problems in Fragile X syndrome.

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

Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome
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. $90,000 GrantEmily Osterweil, PhD Principal Investigator Stephanie Barnes, PhD FRAXA Postdoctoral Fellow University of Edinburgh 2016-2017 FRAXA Research Grant $90,000 over 2 Years A Neuron to Remember: Correcting Imbalances in Fragile X SyndromeUniversity of Edinburgh Researcher Emily Osterweil, PhD, Probes the Brain’s Biochemistry to Correct Imbalances We know the “X” in Fragile X refers to the X chromosome, but it could just as easily refer to the unknown.Such as why do people with Fragile X have an excessive production of new proteins in their brains that lead to imbalances? That question is being dissected in the lab of Emily Osterweil, PhD, chancellor’s fellow, Centre for Integrative Physiology, University of Edinburgh, UK. Dr. Osterweil is usingRead more

Abnormalities of Synaptic Plasticity in the Fragile X Amygdala

Abnormalities of Synaptic Plasticity in the Fragile X Amygdala

With a $110,050 grant from FRAXA Research Foundation from 2005-2016, Dr. Sumantra Chattarji at the National Center for Biological Sciences researched how the amygdala is affected by Fragile X syndrome. Results published.

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Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat Fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).

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Fruit Flies to Model and Test Fragile X Treatments

Fruit Flies to Model and Test Fragile X Treatments

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.

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Analysis of Developmental Brain Dysfunction in Families

Analysis of Developmental Brain Dysfunction in Families

FRAXA Research Foundation is proud to make a grant of $90,000 over 2014-2015 to Margaret King, PhD. The goal of this project is to identify new approaches to clinical trial design for Fragile X pharmaceuticals.

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