FRAXA Drug Validation Initiative (FRAXA-DVI)
The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective preclinical testing to validate investigational and repurposed compounds for Fragile X.
Defining Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists
This study showed that selectively targeting mGluR5 receptors in specific neuronal compartments can correct distinct Fragile X synaptic defects, improving precision therapy.
PIKE as a Central Regulator of Synaptic Dysfunction in Fragile X Syndrome
With $255,000 from FRAXA Research Foundation, Dr. Suzanne Zukin at Albert Einstein College of Medicine studied signalling pathways in Fragile X syndrome.
Fragile X Mutant Mouse Models
With $375,000 in grants from FRAXA, Dr. David Nelson developed an array of advanced mouse models of Fragile X. These models are available at Jackson Labs (JAX).
The Endocannabinoid System in a Mouse Model of Fragile X Syndrome
Fragile X disrupts endocannabinoid signaling. This study in mice demonstrated that correcting it may calm brain hyperexcitability and improve symptoms.
Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome
STEP inhibition reversed behavioral and synaptic Fragile X deficits in mice (Neuropharmacology, 2018), highlighting STEP as a promising treatment target.
Functional Interplay Between FMRP and CDK5 Signaling
FRAXA-funded work showed CDK5 signaling is disrupted in Fragile X. CDK5 drugs are in development for Alzheimer’s so this pathway offers a promising new FX treatment angle.
Glycogen Synthase Kinase-3 (GSK3), Lithium and Fragile X
Dr. Jope found that lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice.
Treatment of Fragile X Syndrome via Dopamine Enhancers and Glutamate Inhibitors
In Fragile X mice, low dopamine signaling and excessive glutamate activity were targeted with dual therapy: dopamine enhancers plus glutamate inhibitors.
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.
A Developmental Switch Exists in the Effects of FMRP
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.
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.
Reward Function in Fragile X Syndrome
Loss of FMRP disrupts dopamine-driven reward function—Fragile X mice show impaired cocaine sensitization and place preference, revealing new plasticity defects.
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.
In Vitro Coherent Network Activity
This work revealed that Fragile X neurons form disordered network dynamics—laying groundwork for using network activity as a treatment-screening metric.
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.
Clinical Trials Outcome Measures
In Fragile X participants, low-dose lithium showed benefits and helped refine biomarkers and behavioral assessments.