Fragile X Clinical Trial of New PDE4D Inhibitor from Tetra

With a $200,043 grant from FRAXA Research Foundation, Dr. Elizabeth Berry-Kravis completed a successful Phase 2 clinical trial of a PDE4 inhibitor for adult men with Fragile X syndrome. This trial treated 30 males, 18-45 years of age with a new PDE4D allosteric inhibitor from Tetra Discovery Partners using a crossover design, so that everyone got active drug for part of the time and placebo for part of the time.

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Functional and Genomic Characterization of Interneurons in the Fmr1-KO Mouse Brain

The brain’s balance is maintained by two types of neurons: those that excite and those that inhibit activity. Like yin and yang, this balance is essential. This team has found fewer than normal inhibitory cells in the brains of Fragile X mice. They are now working to pinpoint this abnormality and find ways to restore the normal balance and function.

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Transcriptional Signatures Sensitive to Cognition-Improving Pharmacological Treatments in Fragile X Syndrome

The Fragile X field needs biomarkers to accurately measure the effects of potential treatments in both Fragile X mice and in humans. Dr. Ozaita and his team have found molecular features in the brain that can serve as an objective signature for the syndrome. They will use this tool to test cannabidiol and two other drugs in mice.

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Repurposing FDA-Approved Drugs to Treat Major Depressive Disorder in Fragile X Syndrome

Did you know that depression is more common in those with autism and/or Fragile X? Even more disturbing is the discovery that current treatments for depression do not work in Fragile X mice. With this grant, the team will work to develop a rapid screening tool to identify FDA-approved drugs which can treat depression in people with Fragile X syndrome.

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Cannabinoids as a Treatment for Fragile X Syndrome

Many people with Fragile X syndrome are hyper-sensitive to sights and sounds, and Electroencephalography (EEG) studies show that there are abnormalities in brain circuits. EEG studies show similar changes in Fragile X mice. So the team will use EEG tests in mice to find which drugs best reduce hypersensitivity. They can then easily move on to human EEG-based clinical trials. What they learn will tell us much more about why people with Fragile X are hypersensitive – and which drugs could best help them.

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Inhibiting Nonsense – Mediated mRNA Decay: A Potential Treatment Approach for Fragile X

All cells have a kind of housecleaning service which sweeps away genetic errors. This is called nonsense-mediated mRNA decay (NMD). With a previous FRAXA grant, this team discovered runaway NMD in cells of Fragile X patients. It’s not yet known how this impacts people with Fragile X. With this grant, Dr. Maquat and Dr. Kurosaki will test drugs which can bring NMD back to normal levels.

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Exploring Drug Repurposing to Restore Hippocampal Function in FXS Mouse Models

A gene’s job is to produce a protein. In Fragile X syndrome, the FMR1 gene is mutated and cannot make FMRP, a protein which shapes connections between nerve cells (neurons) in the brain. These connections are the basis of learning and memory. This team has discovered a mechanism involving FMRP that is absolutely essential to control the connections between neurons. These connections are the basis of learning and memory. They will now test available drugs which directly target this mechanism, to see if they can treat Fragile X syndrome.

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The Role of Astrocyte BMP Signaling in Fragile X Syndrome

Astrocytes are star-shaped cells that make up one fifth of all cells in the human brain. Recently researchers found a specific pathway in astrocytes that is overactive in Fragile X syndrome, and they hope to bring this pathway back to normal with a drug. With this grant, the team will try to correct the pathway in Fragile X mice. The hope is that they will find a new potential treatment approach for Fragile X syndrome.

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