Correcting Defects in Astrocyte Signaling in Fragile X Syndrome
Astrocytes, brain cells which support neurons, do not transmit signals. Fragile X treatment strategies have been proposed based on correction of “astrocyte phenotypes”.
Altered Neural Excitability and Chronic Anxiety in a Mouse Model of Fragile X
With a $35,000 grant from FRAXA, Dr. Peter Vanderklish at Scripps Research Institute, and colleagues, explored the basis of anxiety in Fragile X syndrome.
Development of a High-Content Synapse Assay to Screen Therapeutics for Fragile X Syndrome
This work established a high-content synaptic imaging platform for Fragile X cells to test many candidate drugs for their ability to repair synapse structure and function.
Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome
Dr. Frank Kooy and colleagues conducted a double blind crossover trial of ganaxolone in patients with Fragile X with FRAXA funding. Results of this study were mixed.
Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X
FRAXA Research Foundation awarded $122,000 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.
Fragile X Research Tackles High Anxiety – Peter Vanderklish
Peter Vanderklish studies the brain circuits driving severe anxiety in Fragile X, identifying targets in stress pathways to develop treatments that reduce anxiety and improve daily life.
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.
Sensory Hypersensibility in Fragile X Syndrome and BK Channel Openers
With $366,100 in FRAXA funding, researchers tested BK channel–opening drugs to fix sensory abnormalities in Fragile X mice; early results showed broad behavioral rescue.
Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome
FRAXA-funded research showed nonsense-mediated mRNA decay is overactive in Fragile X, pointing to existing NMD-suppressing drugs like caffeine as potential treatments.
Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome
With this grant from FRAXA, Dr. Peter Vanderklish explored AMPK activators to treat Fragile X. Both metformin and resveratrol, found in red wine, are AMPK activators.
Fruit Flies to Model and Test Fragile X Treatments
Boosting cAMP signaling restores memory and fixes brain-signaling defects in Fragile X models, suggesting diabetes drugs like metformin may help.
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.
Molecular Mechanisms of Cytoskeletal Regulation by FMRP
With FRAXA funding, Dr. Jaffrey linked FMR1 loss to abnormal dendritic spines via RhoA signaling, suggesting RhoA-targeted therapies could help treat Fragile X.
Targeting the Endocannabinoid System in Adult Fragile X Mice
CB1 blockade with rimonabant reversed cognitive, sensory, and seizure symptoms in FXS mice, highlighting the endocannabinoid system as a therapeutic target.
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.
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.
Synaptic Characterization of Human Fragile X Neurons
Stanford scientists used human stem-cell–derived neurons to show that retinoic acid signaling is blocked by Fragile X, revealing a new pathway to target for treatment.
Bcl-xL Inhibition as a Therapeutic Strategy for Fragile X Syndrome
Fragile X neurons show leaky mitochondria and excess Bcl-xL–driven synapses. Targeting this pathway may restore energy balance and healthier brain development.
Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists
Dr. Wong studies how NMDA and mGluR receptors interact to trigger seizures in Fragile X, revealing NR2B-specific blockers as a promising targeted treatment.
Small Molecules To Target r(CGG) Expansions to Treat Fragile X Syndrome
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.
Social Behavior as an Outcome Measure for Fragile X Clinical Trials
FRAXA funding helped identify reliable social behavior tests in Fragile X mice and showed an mGluR5 treatment could improve sociability, guiding future trials.
Translation-Independent Functions of FMRP in Excitability, Synaptic Transmission and Plasticity
Study pinpointed presynaptic calcium dysfunction as the driver of STP defects in Fragile X, and BK channel activation restored normal synaptic signaling.
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.