10 Year Vision for Fragile X Research – Dr. Elizabeth Berry-Kravis & Dr. Patricia Cogram
In this video we hear from FRAXA Investigators Dr. Patricia Cogram, Professor at the University of Chile, and Dr. Elizabeth Berry-Kravis, Professor at Rush University Medical Center as they reflect on the progress that has been made and visualize what they see happening in the next 10 years for people living with Fragile X syndrome.
mRNA Therapy for Fragile X Syndrome
Dr. Kathryn Whitehead helped develop the science behind the COVID-19 vaccines. Her team adapted this technology to deliver the Fragile X mRNA to brain cells.
Sigma-1 Receptor as a Therapeutic Target for Fragile X Syndrome
Researchers will test sigma-1 receptor drugs—like fluvoxamine, which activates this pathway—to see if they can correct Fragile X brain cell abnormalities.
Fragile X Clinical Trial of New PDE4D Inhibitor from Tetra
A $200K FRAXA grant enabled a successful Phase 2 trial of a PDE4D inhibitor for adult men with Fragile X, showing strong cognitive gains without side effects or tolerance.
Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target
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.
Versatile Drug Screening Platform for Fragile X Syndrome
Combinations of drugs may be needed to treat Fragile X syndrome. How can we find the best combinations in the ideal doses? This project tackles this challenge.
Human FMR1 Isoform-Specific Regulation of Translation and Behavior
FMRP has multiple forms, and this team will study which isoforms are most important for brain development. This is key for future FMRP replacement therapies.
Functional and Genomic Characterization of Interneurons in the Fmr1-KO Mouse Brain
The brain’s balance is maintained by two types of neurons: excitatory and inhibitory. This team has found fewer than normal inhibitory cells in Fragile X mice.
Targeting Serotonin 1A Receptors in Fmr1 Knockout Mice
Boosting serotonin 1A receptors may reduce excess brain activity in Fragile X. This study will test serotonin-1A–targeting compounds in mice to guide future treatments.
Transcriptional Signatures Sensitive to Cognition-Improving Pharmacological Treatments in Fragile X Syndrome
This team is defining Fragile X “molecular signatures” to use as biomarkers. They’ll test CBD and other drugs in mice and compare findings to human brain data.
Characterization and Modulation of microRNAs in Fragile X Syndrome
MicroRNAs are disrupted in Fragile X; the team will work to understand this and explore ways to correct it with drugs which directly target microRNAs.
Repurposing FDA-Approved Drugs to Treat Major Depressive Disorder in Fragile X Syndrome
Depression is common in Fragile X, but current antidepressants need FMRP to work. Researchers will screen FDA-approved drugs to find effective options for FXS.
Correcting Fragile X Syndrome Deficits by Targeting Neonatal PKCε Signaling in the Brain
Enhancing PKCε in early development normalized oxytocin, AMPAR signaling, and adult behavior in Fragile X mice, highlighting PKCε as a promising therapeutic target.
Potential Upcoming Advances in Fragile X Research
Dr. Peter Kind, Director of the Patrick Wild Centre and Professor of Developmental Neuroscience at the University of Edinburgh, and Dr. Nahum Sonenberg, James McGill professor of biochemistry at McGill University, share their optimism about the next 10 years of Fragile X research. They discuss where they think the next big discoveries will emerge.
Lovamix: Clinical Trial of Combined Treatment of Minocycline and Lovastatin in Fragile X Syndrome
FRAXA funded the LovaMiX trial of lovastatin + minocycline for Fragile X. 2022 results show safety and support continued study of this dual-target treatment approach.
Reactivating the Fragile X Gene in Young Mice Reverses Symptoms
Fragile X syndrome might be treated by reactivating the gene which is shut down in the syndrome. Researchers were able to reduce FXS symptoms by inserting the FMR1 gene into the brains of young mice.
GABA-A Receptor in Fragile X Syndrome
Published results from Dr. Frank Kooy reveal how GABAA receptor changes may hold the key to treating Fragile X syndrome.
Characterization of a Novel CYFIP1 – Derived Peptidomimetic Restoring the Dysregulated mRNAs Translation: Toward An Innovative Therapeutic Strategy for FXS
This team is designing tiny “peptidomimetic” drugs that mimic FMRP’s function to rebalance protein production in the brain, aiming to treat Fragile X at its source.
FX-Learn Clinical Trial for Children with Fragile X
Thirteen centers across the US enrolled children with Fragile X in a large-scale clinical trial of Novartis AFQ056. Dr. Elizabeth Berry-Kravis and colleagues aim to show that this targeted treatment — an mGluR5 blocker for Fragile X which failed in previous adult human trials — can be better evaluated by studying effects on learning in young children.
Cannabinoids as a Treatment for Fragile X Syndrome
This team uses EEG to study sensory hypersensitivity in Fragile X. By testing drugs in mice, they aim to find treatments that calm brain overactivity.
Clinical Trial of Metformin for Fragile X Syndrome
FRAXA-funded open-label trial found that metformin led to increased GABA-mediated cortical inhibition, suggesting metformin modulates core Fragile X pathways.
Correcting the Brain’s Emotional Memory Center
FRAXA Investigator Dr. Sumatra Chattarji investigated the synaptic basis of deficient conditioned fear and its reversal in Fragile X syndrome rats. Results published.
Purposeful and FRAXA Partnership Leads to Clinical Trial
AI and FRAXA-DVI identified a drug + supplement combo that reversed all Fragile X symptoms in mice. A clinical trial tested this in adults with Fragile X.
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.