Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.
This team was able to establish the endocannabinoid system as a therapeutic target for Fragile X syndrome. They also showed that the system can be targeted with pharmacology.
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.
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.
Wondering which Fragile X trial is right? Eligibility varies, so most families qualify for just one. Talk with your closest clinic to find the best fit.
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.
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.
Using a fruit-fly Fragile X model, researchers screened many drugs quickly to find those that improve behavior, speeding up potential treatment testing.
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.
Fragile X mice show reduced basal cAMP and exaggerated mGluR-LTD; boosting cAMP or blocking specific adenylyl cyclases rescues synaptic and behavioral defects.
Fragile X mice show weakened GABAergic inhibition in key brain regions like the amygdala. Enhancing GABA_A receptor activity reduced hyperactivity and improved inhibition.
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.
A clinical trial of minocycline in children with Fragile X found significantly better global improvement vs. placebo, supporting its safety and potential.
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.
