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.
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.
Ion channel defects (“channelopathies”) in Fragile X disrupt neuron firing and network balance. This study maps these channel changes to guide targeted treatments.
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.
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.
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).
A clinical trial of minocycline in children with Fragile X found significantly better global improvement vs. placebo, supporting its safety and potential.
The team screened compounds with Neuropharm (UK) looking for compounds to reactivate the FMR1 gene. They also analyzed unmethylated full mutation cell lines.
Researchers found that FMRP-deficient neural stem cells divide too much and fail to mature properly; screening compounds revealed candidates restoring normal behavior.
