Inhibiting Nonsense – Mediated mRNA Decay: A Potential Treatment Approach for Fragile X
This team previously discovered runaway nonsense-mediated mRNA decay (NMD) in cells of Fragile X patients. They will now test drugs to reduce NMD.
Contribution of Microglia to the Therapeutic Effects of Metformin and Adiponectin in Fragile X Syndrome
Why are some with Fragile X always hungry or overweight, yet rarely diabetic? This team is studying metabolism and testing treatments like metformin and diet.
Alternative Splicing in White Blood Cells: A Biomarker for Fragile X Syndrome
This team found 1,600 blood-based Fragile X biomarkers that vary by individual—opening the door to personalized treatment and better ways to measure progress.
The Role of Astrocyte BMP Signaling in Fragile X Syndrome
Researchers found a pathway in astrocytes that is overactive in Fragile X syndrome, and they hope to bring this pathway back to normal with a drug.
Identifying Cellular and Molecular Signatures in Human Neurons That Distinguish Fragile X Syndrome Patients with Divergent EEG Profiles
Just as Fragile X affects individuals differently, medications do as well. This project aims to bring personalized medicine to Fragile X syndrome.
Auditory Dysfunction in Fragile X Syndrome in a Mouse Model of Fragile X
FRAXA-funded studies found Fragile X mice show altered auditory circuit function with delayed startle timing and reduced prepulse inhibition, mirroring human sound sensitivity.
Positive Results Reported in Phase II Fragile X Clinical Trial of PDE4D Inhibitor Zatolmilast from Tetra Therapeutics
Tetra Therapeutics announces the first unequivocally positive phase 2 clinical trial in Fragile X syndrome. The results do not depend on carving out a subset of patients or post hoc analysis.
Genome-wide Screen for FMR1 Reactivation in Human FXS Neural Cells
This team aims to turn the FMR1 gene back on in Fragile X by identifying factors that reactivate the silenced gene and restore production of the missing FMRP protein.
MicroRNAs as Biomarkers in Fragile X Syndrome
The team at Johns Hopkins University studied groups of small RNAs, known as microRNAs, which are greatly decreased in brain tissue of Fragile X mice vs. normal controls.
Auditory System Dysfunction and Drug Tolerance in the Fragile X Mouse
A $90K FRAXA grant will help uncover why Fragile X causes sound hypersensitivity and test ways to correct brain circuit dysfunction linked to auditory overload.
MicroRNA Mediated Astroglial GLT1 Dysregulation in Fragile X
The team studied how glial cells, especially astrocytes, affect Fragile X. They tested microRNAs to restore GLT1 and reduce excess glutamate linked to brain hyperexcitability.
Cholesterol-Dependent Changes in Fragile X Astrocytes
Astrocytes and cholesterol metabolism are altered in Fragile X. This research uncovers how these changes affect the brain and may reveal new treatment targets like lovastatin.
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.
Targeting Adiponectin to Treat Fragile X Syndrome
Boosting adiponectin, a hormone that regulates metabolism, may improve cognition and behavior in Fragile X. Early results suggest it can restore brain plasticity.
Biomarker Discovery and Validation for Fragile X Syndrome
This grant supported discovery of protein-based biomarkers for Fragile X to create objective outcome measures that translate from mouse studies to human trials.
Targeting Mitochondria in Human Fragile X Syndrome Neurons
Fragile X brain cells have fewer, smaller mitochondria. This team tested mitochondria-boosting drugs that improved symptoms in mice to see if they can help humans.
Correcting Sensory Processing in Fragile X Mice by Modulating Kv3.1
FRAXA funded UCLA research on a Kv3.1-targeting drug to ease sensory issues in Fragile X. This work built on Yale-led work now also being pursued by Autifony Therapeutics.
Which is the right FMRP for Therapeutic Development of Fragile X Syndrome?
Many forms of FMRP exist in the brain. This project aims to pinpoint which versions of the protein are most critical to restore for effective Fragile X treatments.
Developmental Profile of Glutamatergic Synapses in Fragile X
A FRAXA fellowship helped reveal how glutamate receptors at synapses develop differently in Fragile X, offering clues to improve learning and memory.
Reintroducing FMRP via Tat to Reduce Symptoms of Fragile X Syndrome
A FRAXA-funded team found that a shortened FMRP protein, delivered with a Tat “carrier,” restores brain signaling and improves behavior in Fragile X mice.
Novel Modulators of Potassium Channels to Treat Fragile X
FRAXA-funded Yale research showed disrupted Kv3.1 and Slack potassium channels impair neuronal timing in Fragile X. Published findings support Kv3.1 as a treatment target.
Autophagy is a Novel Therapeutic Target of Impaired Cognition in Fragile X Syndrome
FRAXA’s $90K grant enabled Dr. Zukin to link impaired autophagy to Fragile X. Boosting autophagy restored synaptic proteins and reversed cognitive deficits in mice.
NKCC1 Inhibitor Bumetanide Corrects Synaptic and Circuit Hyperexcitability in Fragile X Mouse Model
Dr. Anis Contractor and Dr. Qionger He investigated the potential of the available drug bumetanide to correct altered GABA signalling in a mouse model of Fragile X syndrome.
Research Points to Drugs which Inhibit PDE to Treat Fragile X
FRAXA-funded work identified PDE enzymes as key targets in Fragile X, showing that PDE inhibitors can fix signaling and boost synaptic function. PDE4D trials are underway.