Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome

Inhibitors 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.

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GABA-A Receptor in Fragile X Syndrome

GABA-A Receptor in Fragile X Syndrome
FRAXA Research Foundation funded studies under the direction of Dr. Frank Kooy at the University of Antwerp in Belgium. $210,000 GrantsFrank Kooy, PhD Principal Investigator University of Antwerp, Belgium FRAXA Research Grants $45,000 in 2010 $100,000 in 2007-8 $65,000 in 1999-2000 by Frank Kooy, PhD Absence of a single protein, FMRP, in Fragile X patients leads to a cascade of molecular events in brain cells. To find out which other genes are involved the clinical symptoms, we have been looking for genes that are differentially expressed in Fragile X syndrome. One of the genes specifically underexpressed is part of the GABAA receptor. As GABA-A receptors are the main inhibitory receptors in the brain, involved in processes like anxiety, mood swings, sleep and cognition, processes also disturbed in Fragile X patients, we followed up on this finding. In subsequent studies, we demonstrated abnormalities in expression levels of multiple parts of the GABA-ARead more

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Studies have shown that the function of inhibitory networks is disturbed in Fragile X. This abnormality is not well understood but appears to be secondary to abnormalities in metabotropic glutamate and endocannabinoid systems. With a $90,000 grant from FRAXA in 2013-2014, Dr. Molly Huntsman’s team examined how these networks interact and how inhibitory deficits can best be remedied.

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Functional Interplay Between FMRP and CDK5 Signaling

Functional Interplay Between FMRP and CDK5 Signaling

With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the Fragile X protein, FMRP, in the Fragile X mouse model.

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Computational Analysis of Neural Circuit Disruption in Fragile X Model Mice

Computational Analysis of Neural Circuit Disruption in Fragile X Model Mice

Computer modeling of the brain offers the hope of predicting how the brain responds to varying conditions, but these models have been rather primitive until recently. The Sejnowski team at the Salk Institute, who specialize in computational models of neural networks, will take the results of previous FRAXA-funded projects and incorporate them into their advanced computer models of brain function.

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Synaptic Characterization of Human Fragile X Neurons

Synaptic Characterization of Human Fragile X Neurons

With a $90,000 grant from FRAXA Research Foundation over 2013-14, Dr. Marius Wernig and Dr. Samuele Marro at Stanford analyzed homeostatic plasticity and regulation of synaptic strength by retinoic acid. If the results are encouraging, they will move forward with testing whether available RA antagonists can alleviate observed abnormalities in these cells.

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Bcl-xL Inhibition as a Therapeutic Strategy for Fragile X Syndrome

Bcl-xL Inhibition as a Therapeutic Strategy for Fragile X Syndrome

Scientists have found increases in the numbers of neurons in brain regions of autistic children, suggesting a problem in developmental programmed cell death pathways. One of the most important effectors of neuronal survival during brain development is the “anti-cell death” protein Bcl-xL. While the normal function of Bcl-xL is to maintain a healthy number of neurons and synapses, over-expressed Bcl-xL can cause an overabundance of synaptic connections. This may be happening in Fragile X.

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Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists

Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists
With a $90,000 grant from the FRAXA Research Foundation, Dr. Robert Wong is investigating how seizures are generated in Fragile X neurons. More generally, he is looking at how synapses are modified to enable learning and memory and how this process is impaired in Fragile X. $90,000 Grant Robert Wong, PhD Principal Investigator State University of New York 2013-2014 FRAXA Research Grant $90,000 over 2 Years Abnormal increases in sensitivity of a type of glutamate receptor (group I mGluR) cause brain malfunction, including epilepsy, in Fragile X syndrome (FXS). We are examining a newly uncovered regulation of this increased group I mGluR sensitivity by a second type of glutamate receptor, the NMDA receptor. By looking at audiogenic seizures in FXS model mice, NMDA receptor blockers were found to robustly suppress these seizures at the young developmental stage. In contrast, the same antagonists activated seizure activities, normally dormant, in adult FXS model mice and in a CGGRead more

Translation-Independent Functions of FMRP in Excitability, Synaptic Transmission and Plasticity

Translation-Independent Functions of FMRP in Excitability, Synaptic Transmission and Plasticity

With a $140,000 grant from FRAXA Research Foundation, Dr. Vitaly Klyachko and team at Washington University explored STP (short-term plasticity) in Fragile X, namely looking at presynaptic calcium dynamics as a major underlying cause of the STP defects.

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Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

With a $157,000 grant from the FRAXA Research Foundation in 201202013, Dr. Kendal Broadie and Dr. Cheryl Gatto worked to define the distinct but also overlapping roles for MMP-1 and MMP-2 in synaptic structural and functional development. In drug studies with Fragile X fruit flies, they will be testing a range of MMPIs in drug treatments to compare effectiveness during development and at maturity, in order to define the contributions of FXS developmental impairments and adult recovery/plasticity.

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Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice

Endocannabinoid 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.

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Is There a Developmental Switch in the Effects of FMRP?

Is There a Developmental Switch in the Effects of FMRP?

With a $474,300 grant from FRAXA Research Foundation from 2000-2013, 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.

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Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

With a $66,000 grant from FRAXA Research Foundation in 2013, Dr. Lucia Ciranna and her team from the Universita di Catania tested if specific serotonins could reverse abnormal phentotypes found in Fragile X syndrome. 

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The Endocannabinoid System in a Mouse Model of Fragile X Syndrome

The Endocannabinoid System in a Mouse Model of Fragile X Syndrome

With a $128,500 grant over 2011-2013 from FRAXA Research Foundation, Drs. Bradley Alger and and Ai-Hui Tang at the University of Maryland researched endocannabinoid pathways in Fragile X.

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Small Rho GTPases, a Potential Therapeutic Target for Fragile X Syndrome

Small 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.

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Evaluation of CamKII Dependent Regulation of mGluR5-Homer Scaffolds as a Potential Therapeutic for Fragile X Syndrome

Evaluation of CamKII Dependent Regulation of mGluR5-Homer Scaffolds as a Potential Therapeutic for Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation, Dr. Kimberly Huber and Dr. Weirui Guo at the University of Texas at Soutnwestern investigated the roles of Homer and CaMKII in Fragile X syndrome.

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Synaptic Actin Signaling Pathways in Fragile X

Synaptic 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.

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Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value

Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value

With a $90,000 grant from the FRAXA Research Foundation, Dr. Gary Bassell and his team at Emory University explored the PI3K/mTOR signaling complex in FXS via genetic and pharmacologic rescue approaches, to reduce the enzymatic function of specific components of this complex pathway in an FXS mouse model.

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Reward Function in Fragile X Syndrome

Reward Function in Fragile X Syndrome

With a $82,500 grant from FRAXA Research Foundation in 2011-2012, Dr. Christopher Cowan and Dr. Laura Smith explored the role of specific signaling pathways in drug-related behavioral deficits, including determining the role, if any, of known impairments in the Fragile X brain.

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Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice

Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice
With this $90,000 award, Dr. Zhang and Principal Investigator Dr. Andreas Frick at Neurocentre Magendie in France investigated channelopathies using Fragile X mice. $90,000 GrantAndreas Frick, PhD Principal Investigator Yu Zhang, PhD FRAXA Postdoctoral Fellow Neurocentre Magendie 2010-11 FRAXA Research Grant $90,000 over 2 Years   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. The mammalian neocortex is central for processes as diverse as sensory information processing, perception or control of motor activity, and cortical defects have devastating neurological and psychiatric consequences. In humans, the consequencesRead more

Role of JNK in FMRP Regulated Translation in Fragile X Syndrome

Role of JNK in FMRP Regulated Translation in Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation over 2 years, Dr. Michael Wilhelm and his team at the University of Wisconsin studied a protein known as JNK, which is observed to be abnormally regulated in Fragile X. Like FMRP, it is involved in regulating dendritic protein synthesis, and so it may be a target for drug therapy in Fragile X.

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Serotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice

Serotonergic 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).

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Efficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila

Efficient 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.

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