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.
Analysis of Developmental Brain Dysfunction in Families
No strong behavioral similarities were found between parents and children with Fragile X, indicating family history may not guide clinical trial recruitment.
Effects of Metformin in Fmr1 Knockout Mouse Model of Fragile X Syndrome
Metformin, a safe diabetes drug, activates AMPK to rebalance protein synthesis. FRAXA-funded work investigated its potential to treat Fragile X.
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.
Phase 1 Clinical Trial of Mega Green Tea Extract in Fragile X Syndrome
An early trial of green tea extract EGCG improved cognition in Fragile X. It targets ERβ and reduces overactive PI3K/mTOR/ERK signaling linked to FXS symptoms.
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.
Computational Analysis of Neural Circuit Disruption in Fragile X Model Mice
FRAXA-funded researchers used advanced computer models to uncover how FXS brain circuits change and predict which treatments may correct them. Results published.
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.
Potassium Channel Modulators to Treat Fragile X
FRAXA-backed Yale discoveries tied Fragile X to Kv3.1/Slack channel defects—leading to a partnership with Autifony to develop targeted treatments.
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.
Development of a Novel GABA-A Agonist in Fragile X Syndrome
FRAXA funded analysis of a selective GABA-A drug for Fragile X, leading to a clinical trial at Cincinnati Children’s to test this potential treatment.
The mTOR Pathway in Fragile X Syndrome
FRAXA-funded research showed that blocking S6K1 in Fragile X mice improves social, behavioral, and physical symptoms.
Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome
Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.
Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X
With FRAXA funding, Dr. Khaleel Razak and Dr. Iryna Ethell explored robust biomarkers relevant to the FXS and the efficacy of minocycline treatment.
Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice
FRAXA-funded studies found faulty endocannabinoid signaling in Fragile X brain circuits for reward and emotion, and boosting 2-AG restored normal function.