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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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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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 over 2016-2018, 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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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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FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

Mis-regulation of activity-dependent protein synthesis is one of the major cellular abnormalities found in Fragile X. Upstream neuronal signaling regulates a large cluster of enzymes called the mTORC1 complex, which in turn regulates protein synthesis. This complex is also controlled by cellular energy levels via the metabolic sensor AMP-activated Protein Kinase (AMPK). AMPK is a highly conserved kinase that is activated under conditions of energy stress, when intracellular ATP levels decline and intracellular AMP increases.

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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.

Paul Lombroso, PhD, Yale University, FRAXA InvestigatorRead 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

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.

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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 2012-2013, 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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Research Grants to Dr. Kimberly Huber 2000-2010

Research Grants to Dr. Kimberly Huber 2000-2010

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.

Kimberly Huber, Ph.D., FRAXA InvestigatorRead more

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 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 Southwestern investigated the roles of Homer and CaMKII in Fragile X syndrome.

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A Developmental Switch Exists in the Effects of FMRP

A 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.

Dr. Kimberly HuberRead more