Small Rho GTPases, a Potential Therapeutic Target for Fragile X Syndrome
Dr. MariVi Tejada from the University of Houston tested several potential therapeutic compounds in an attempt to rescue function in the mouse model of Fragile X.
Evaluation of CamKII Dependent Regulation of mGluR5-Homer Scaffolds as a Potential Therapeutic for Fragile X Syndrome
Disrupted mGluR5–Homer scaffolding in Fragile X is linked to excess CaMKII activity. Restoring this interaction could rebalance signaling and improve symptoms.
Ab-Mediated Translation in Fragile X Syndrome
This work found amyloid precursor protein (APP) overexpression and increased β-amyloid in Fragile X mice, implicating Alzheimer-related pathways in FXS pathology.
Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value
Targeting the PI3K/mTOR cascade — specifically p110β — in Fragile X mice reversed neural and behavioral dysfunctions, validating it as a treatment pathway.
A Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse
This work revealed small-molecule metabolic changes in Fragile X brains and is using them to build a drug-efficacy index for screening therapies.
Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice
Researchers found that Fragile X brain circuits show faulty ion channel activity (channelopathies). Fixing these channels may restore normal brain signalling.
Role of JNK in FMRP Regulated Translation in Fragile X Syndrome
JNK kinase is abnormally active in Fragile X model mice and directly regulates mGluR-dependent translation of FMRP targets, pointing to JNK as a therapeutic target.
Serotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice
Dr. Zhu examined how serotonin-targeting drugs such as Buspar and Abilify influence synaptic plasticity, including LTP and LTD.
Efficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila
Using a fruit-fly Fragile X model, researchers screened many drugs quickly to find those that improve behavior, speeding up potential treatment testing.
Channelopathies: Altered Ion Channels in Fragile X Syndrome
Ion channel defects (“channelopathies”) in Fragile X disrupt neuron firing and network balance. This study maps these channel changes to guide targeted treatments.
Role of Excessive Protein Synthesis in the Ontogeny of FXS
Excessive neuronal protein synthesis is not just a symptom but appears to cause early synaptic wiring defects in Fragile X — highlighting translation control as a key target.
Altered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome
Loss of FMRP leads to excess synthesis of the scaffold protein Shank1 at dendrites. Elevated Shank1 may impair synaptic pruning and drive Fragile X spine pathology.
Manipulating Basal and mGluR-Stimulated cAMP Level in FXS Model Mice
Fragile X mice show reduced basal cAMP and exaggerated mGluR-LTD; boosting cAMP or blocking specific adenylyl cyclases rescues synaptic and behavioral defects.
GABAergic Inhibitory Function in Fragile X Syndrome
Fragile X mice show weakened GABAergic inhibition in key brain regions like the amygdala. Enhancing GABA_A receptor activity reduced hyperactivity and improved inhibition.
Correcting Fragile X Syndrome by Inhibiting the Synaptic RNA-Binding Protein CPEB1
The Richter lab found that CPEB1 knockdown in Fmr1 KO mice normalized excessive protein synthesis and improved synaptic and memory problems tied to Fragile X.
The Slack Potassium Ion channel is a Therapeutic Target for Fragile X
With $282,000 in funding from FRAXA Research Foundation, Dr. Leonard Kaczmarek and colleagues explored association of Slack channels with the Fragile X protein (FMRP).
Reactivation of the FMR1 Gene
The team screened compounds with Neuropharm (UK) looking for compounds to reactivate the FMR1 gene. They also analyzed unmethylated full mutation cell lines.
Small Molecule Screen Using Fragile X Neural Stem Cells
Researchers found that FMRP-deficient neural stem cells divide too much and fail to mature properly; screening compounds revealed candidates restoring normal behavior.
Neuromotor Outcome Measures for Clinical Trials in Fragile X Syndrome
Drs. Nicole Tartaglia and Tracey Stackhouse advanced neuromotor testing for Fragile X, paving the way for better-targeted clinical trials.
The Role of FMRP and Small, Non-Coding RNAs in Translation
Drs. Henri Tiedge and Jun Zhong investigated how BC1 RNA could restore balance in Fragile X brains, pointing toward RNA-targeted treatments.
Small Molecule Modulators of Lithium for Treatment of Fragile X Syndrome
With a $219,500 FRAXA grant, Dr. Stephen Haggarty at Harvard/MIT used patient-derived stem cells to screen drugs targeting GSK3, aiming to enhance lithium therapy.
Developing Fragile X Treatments in Fruit Flies and Mice
FRAXA’s $380K grant supported Drs. McBride, Jongens, and Choi in validating Fragile X treatments in mice to prepare for trials. Findings published.
Genome-wide Epigenetic Markers in Fragile X
Dr. Miklos Toth’s FRAXA-funded work at Cornell University examined how epigenetic factors shape the severity of Fragile X symptoms.
Role of Matrix Metalloproteinases (MMP-9) in Fragile X
With a $220,000 FRAXA grant, Dr. Iryna Ethell’s team at UC Riverside uncovered MMP-9’s role in Fragile X—leading to a major treatment strategy using minocycline.