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.
Ion channel defects (“channelopathies”) in Fragile X disrupt neuron firing and network balance. This study maps these channel changes to guide targeted treatments.
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.
This paper shows that MMP-9 dysregulation is a critical part of the pathology of Fragile X, and MMP-9 should be considered a major treatment target for 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.
Dr. Claudia Bagni’s team discovered that FMRP can act as a master switch in aggressive breast cancer, controlling proteins that drive invasion and metastasis.
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.
Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.
This team was able to establish the endocannabinoid system as a therapeutic target for Fragile X syndrome. They also showed that the system can be targeted with pharmacology.
