With this FRAXA grant, Dr. Carolyn B. Smith and Dr. Rache Sare at the National Institute of Mental Health investigated the basis of sleep problems in Fragile X syndrome.
Drs. Emily Osterweil and Stephanie Barnes investigated NMDA receptor signaling and how rebalancing protein synthesis could correct Fragile X brain abnormalities.
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.
No strong behavioral similarities were found between parents and children with Fragile X, indicating family history may not guide clinical trial recruitment.
Fragile X disrupts endocannabinoid signaling. This study in mice demonstrated that correcting it may calm brain hyperexcitability and improve symptoms.
STEP inhibition reversed behavioral and synaptic Fragile X deficits in mice (Neuropharmacology, 2018), highlighting STEP as a promising treatment target.
With FRAXA funding, Dr. Jaffrey linked FMR1 loss to abnormal dendritic spines via RhoA signaling, suggesting RhoA-targeted therapies could help treat Fragile X.
CB1 blockade with rimonabant reversed cognitive, sensory, and seizure symptoms in FXS mice, highlighting the endocannabinoid system as a therapeutic target.
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.
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.
FRAXA-funded researchers used advanced computer models to uncover how FXS brain circuits change and predict which treatments may correct them. Results published.
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.
Fragile X neurons show leaky mitochondria and excess Bcl-xL–driven synapses. Targeting this pathway may restore energy balance and healthier brain development.
Dr. Wong studies how NMDA and mGluR receptors interact to trigger seizures in Fragile X, revealing NR2B-specific blockers as a promising targeted treatment.
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.
FRAXA funding helped identify reliable social behavior tests in Fragile X mice and showed an mGluR5 treatment could improve sociability, guiding future trials.
Study pinpointed presynaptic calcium dysfunction as the driver of STP defects in Fragile X, and BK channel activation restored normal synaptic signaling.
Dr. Jope found that lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice.
