Pharmacological Tolerance in the Treatment of Fragile X Syndrome
FRAXA funded MIT work to probe tolerance to key Fragile X drugs, including mGluR5 inhibitors and arbaclofen, and to identify ways to sustain long-term treatment benefits.
Repurposing Study II: Evaluating Combinations of Drugs to Treat Fragile X
FRAXA partnered with Healx to use AI to find approved drugs and drug combos that could treat Fragile X. Top candidates are now being tested in Fragile X models.
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.
Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers
University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, explored drug combinations to limit hypersensitivity to sounds in Fragile X mice.
Targeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells
FRAXA funded Dr. Peter Todd to use CRISPR to reactivate FMR1. Published results confirmed restored gene expression, a big step toward disease-modifying therapy.
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.
Investigating Gene Reactivation to Treat Fragile X Syndrome
With a $180,000 grant from FRAXA Research Foundation, Dr. Jeannie Lee and her team at Harvard are working to reactivate the gene that is silenced in Fragile X syndrome.
Prefrontal Cortex Network (PFC) Dynamics in Fragile X Syndrome
The team has shown that Fragile X mice have major prefrontal cortex deficits in Fragile X mice. Finding ways to overcome this could reveal new intervention strategies.
Prefrontal Cortex Network (PFC) Dynamics in Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Daniel Johnston and Dr. Jenni Siegel at the University of Texas at Austin are analyzing pre-frontal cortex (PFC) dysfunction in the Fragile X model. They have preliminary evidence that Fragile X mice are severely impaired in a prefrontal cortex (PFC)-dependent task.
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”.
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.
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.
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).
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.
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.
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.
Clinical Trials Outcome Measures
There is a critical need for reliable biomarkers and clinical outcome measures for Fragile X syndrome. Treatment trials depend on this.
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.
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.
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.
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.