Dr. Wong studies how NMDA and mGluR receptors interact to trigger seizures in Fragile X, revealing NR2B-specific blockers as a promising targeted treatment.
FRAXA-funded scientists created small molecules that target the CGG repeat “off-switch” in Fragile X, aiming to restore the missing FMRP protein at its source.
FRAXA funding helped identify reliable social behavior tests in Fragile X mice and showed an mGluR5 treatment could improve sociability, guiding future trials.
Study pinpointed presynaptic calcium dysfunction as the driver of STP defects in Fragile X, and BK channel activation restored normal synaptic signaling.
Dr. Jope found that lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice.
Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.
FRAXA-funded studies found faulty endocannabinoid signaling in Fragile X brain circuits for reward and emotion, and boosting 2-AG restored normal function.
In Fragile X mice, low dopamine signaling and excessive glutamate activity were targeted with dual therapy: dopamine enhancers plus glutamate inhibitors.
This project developed human stem cell and mouse models to test FMR1 gene reactivation in the brain, advancing future gene therapy strategies for Fragile X.
With FRAXA funding the team found that activating 5-HT7 receptors reversed excess mGluR-LTD in Fragile X mice, pointing to a new route to fix synapses.
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.
Disrupted mGluR5–Homer scaffolding in Fragile X is linked to excess CaMKII activity. Restoring this interaction could rebalance signaling and improve symptoms.
Fragile X research found that FMRP’s role in synapse development changes with age—early on it builds synapses, later it removes them—via MEF2 signaling.
This work found amyloid precursor protein (APP) overexpression and increased β-amyloid in Fragile X mice, implicating Alzheimer-related pathways in FXS pathology.
Targeting the PI3K/mTOR cascade — specifically p110β — in Fragile X mice reversed neural and behavioral dysfunctions, validating it as a treatment pathway.
Loss of FMRP disrupts dopamine-driven reward function—Fragile X mice show impaired cocaine sensitization and place preference, revealing new plasticity defects.
Researchers found that Fragile X brain circuits show faulty ion channel activity (channelopathies). Fixing these channels may restore normal brain signalling.
This work revealed that Fragile X neurons form disordered network dynamics—laying groundwork for using network activity as a treatment-screening metric.
