With $210,000 in grants from FRAXA over 1999-2010, Dr. Frank Kooy has studied the involvement of the GABAergic system in Fragile X syndrome, at the University of Antwerp, Belgium.
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Defining 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).
Read moreMechanisms 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.
Read moreAltered 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.
Read moreDevelopment 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.
Read morePIKE as a Central Regulator of Synaptic Dysfunction in Fragile X Syndrome
With $255,000 from FRAXA Research Foundation, Dr. Suzanne Zukin at Albert Einstein College of Medicine studied signalling pathways in Fragile X syndrome.
Read moreFragile X Mutant Mouse Models
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.
Read moreAbnormalities 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.
Read moreFruit 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.
Read moreInhibitors of STEP as a Novel Treatment of Fragile X Syndrome
With a $349,000 grant from FRAXA Research Foundation from 2008-2015, Dr. Paul Lombroso and his team at Yale University researched if inhibiting STEP could reduce behavioral abnormalities in Fragile X syndrome. Results published.
Read moreGlycogen Synthase Kinase-3 (GSK3), Lithium and Fragile X
With $208,000 in funds from FRAXA Research Foundation, Dr. Richard Jope and his team at the University of Miami tested whether newly developed, highly specific inhibitors of GSK3 can reduce behavioral abnormalities in Fragile X mice.
Read moreThe mTOR Pathway in Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation over 2012-2013, Dr. Eric Klann and Postdoctoral Fellow Dr. Aditi Bhattacharrya of New York University investigated alterations in the mTOR pathway in Fragile X syndrome – which is also known to be defective in several forms of autism. Their work was published in September 2012 and received international attention.
Read moreEndocannabinoid Mediated Synaptic Plasticity in Fragile X Mice
With a $90,000 grant from FRAXA Research Foundation over two years, Drs. Olivier Manzoni and Daniela Neuhofer researched the relationship between Fragile X syndrome and the areas of the brain that are involved in reward processing, regulation of emotional behavior and emotional memory as well as attention, planning and working memory.
Read moreTreatment of Fragile X Syndrome via Dopamine Enhancers and Glutamate Inhibitors
FRAXA Awards $50,000 in 2011 and $50,000 in 2010 to Patricia Cogram, PhD for treatment of Fragile X syndrome via Dopamine Enhancers and Glutamate Inhibitors. This project aims to follow up our and others observations that the dopamine receptor is under expressed in the Fragile X syndrome and thus determine the effectiveness of targeted pharmacological treatments in Fragile X syndrome.
Read moreTargeting mGluR-LTD to Treat Fragile X Syndrome
With grants from FRAXA Research Foundation from 2000-2010, Dr. Kimberly Huber and her team at the University of Texas conducted several studies on the relationship between mGluR5 and Fragile X syndrome. Dr. Huber made the original discovery of the mGluR Theory of Fragile X when she was a postdoctoral fellow in the lab of Dr. Mark Bear, with her first FRAXA grant in 2000.
Read moreSmall Rho GTPases, a Potential Therapeutic Target for Fragile X Syndrome
With $384,345 in grants from FRAXA Research Foundation, Dr. MariVi Tejada from the University of Houston focused on a particularly promising point of intervention in pathways of brain receptors, and tested several potential therapeutic compounds in an attempt to rescue function in the mouse model of Fragile X.
Read moreA Developmental Switch Exists in the Effects of FMRP
With a $90,00 grant from FRAXA Research Foundation for 2010-2011, Dr. Kimberly Huber and her team at the University of Texas at Southwestern found that there is a developmental switch of postsynaptic FMRP on synaptic function. This switch is controlled by MEF2 transcriptional activity. Proper synapse maturation and elimination is crucial for the establishment of appropriate neural circuits that underlie sensory processing and cognition. Neuron of Fragile X patients as well as in the mouse model of Fragile X, Fmr1 KO mice, display more dendritic spines, the point of contact for excitatory synapses, as well as long and thin filopodia resembling immature spines. This suggests Fragile X mental retardation protein (FMRP) has a role in promoting synapse maturation and elimination.
Read moreSynaptic Actin Signaling Pathways in Fragile X
With a $163,356 grant from FRAXA Research Foundation in 2010-12, Dr. Scott Soderling and Dr. Hwan Kim at Duke University bred the standard mouse model of Fragile X syndrome to their lines of mice that express reduced levels of several key proteins that modulate synaptic actin. These compound mutant mice were compared to FXS mice to determine if genetically impairing pathways to the actin cytoskeleton can rescue deficits in the FXS mice.
Read moreA Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse
Dr. Davidovic has been examining changes in metabolism in various brain regions that are affected in Fragile X patients. She has defined a brain-specific metabolic signature of FXS and is testing treatment strategies to restore normal levels of these metabolites.
Read moreInherited Channelopathies in Cortical Circuits of Fmr1 KO Mice
With this two year award of $90,000, Dr. Zhang and Principal Investigator Dr. Andreas Frick at Neurocentre Magendie in France investigated channelopathies using Fragile X mice. Many other proteins are misregulated as a result of the absence of FMRP. It is known that many ion channels, the pores in the cell membrane which allow neurons to conduct electrical impulses, have altered levels in Fragile X. This state is sometime called a “channelopathy” in the pharma world. This group is studying the effect of specific alterations in ion channels, and potential therapeutic effects of drugs which open and close these channels.
Read moreSerotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice
With $306,000 in grants from FRAXA Research Foundation, Dr. Julius Zhu from the University of Virginia examined the effects of several drugs such as Buspar and Abilify which manipulate specific serotonin receptors and the effect that has on synaptic plasticity (LTP and LTD).
Read moreEfficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila
With a $112,250 grant from FRAXA Research Foundation over 3 years, Dr. Efthimios Skoulakis and his team from the Institute of Cellular and Developmental Biology conducted the first FRAXA project in Greece, where they developed a speedy new test for learning problems in fruit flies, which allowed them to test a number of drugs that are potential Fragile X treatments.
Read moreChannelopathies: Altered Ion Channels in Fragile X Syndrome
With a $95,000 grant from FRAXA Research Foundation from 2010-2011, Dr. Daniel Johnston and Dr. Darrin Brager at the University of Texas at Austin investigated alterations in ion channels in Fragile X syndrome. They explored potential therapeutic effects of drugs which open and close these channels. Results published.
Read moreRole of Excessive Protein Synthesis in the Ontogeny of FXS
With a $90,000 grant from FRAXA Research Foundation in 2010-2011, Dr. Mark Bear and Dr. Miquel Bosch tested the simple hypothesis that the excessive rate of protein synthesis is not a consequence but the primary cause of the structural alterations occurring in Fragile X syndrome.
Read moreAltered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome
With a $106,800 grant from FRAXA Research Foundation over 2 years, Drs. Stephan Kindler and Hans-Jurgen Kreieinkamp studied a protein, Shank1, which is overabundant in Fragile X syndrome.
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