In Their Own Words: Reports From the International Fragile X Workshop

In Their Own Words: Reports From the International Fragile X Workshop

The 18th International Fragile X and Related Neurodevelopmental Disorders Workshop in Quebec, Canada, was a great success, featuring Fragile X much more heavily than any previous meeting in this series! We asked our speakers to summarize their work in their own words. These brief updates from researchers investigating Fragile X.

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Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI)

Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI)

The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective preclinical testing of potential new Fragile X treatments. FRAXA has funded FRAXA-DVI for $50,000 or more per year since 2012.

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Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation funded during 2014-2015, Dr. Frank Kooy and colleagues at the University of Antwerp are conducting a double blind crossover trial of ganaxolone in patients with Fragile X syndrome. Results of this study were mixed (see Marinus: Results from Phase 2 Exploratory Clinical Study Support Continued Development of Ganaxolone in Fragile X Syndrome.

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A Neuron to Remember: Correcting Imbalances in Fragile X Syndrome

A Neuron to Remember: Correcting Imbalances in Fragile X Syndrome
FRAXA Fellowship Awarded May 2016, Renewed May 2017 Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome Principal Investigator Emily Osterweil, PhD Postdoctoral Fellow Stephanie Barnes, PhD University of Edinburgh $90,000 over 2 years University of Edinburgh Researcher Emily Osterweil, PhD, Probes the Brain’s Biochemistry to Correct Imbalances We know the “X” in Fragile X refers to the X chromosome, but it could just as easily refer to the unknown.Such as why do people with Fragile X have an excessive production of new proteins in their brains that lead to imbalances? That question is being dissected in the lab of Emily Osterweil, PhD, chancellor’s fellow, Centre for Integrative Physiology, University of Edinburgh, UK. Dr. Osterweil is using insights from previous experiments to identify new treatment strategies for Fragile X. Her goal is to understand the biochemistry of the brain better. She aims to correct those imbalances byRead more

Treating Sleep Disorders in Fragile X Syndrome

Treating Sleep Disorders in Fragile X Syndrome
University of Wisconsin senior scientist Cara Westmark, PhD, studies the effect of promising therapeutics on sleep in Fragile X mice Your child finally falls asleep. You quickly celebrate before quietly turning to your favorite book or another episode of Game of Thrones. You tiptoe to bed. Exhausted, you slowly fall asleep. Enter deep REM. Minutes later, you are awoken loudly. Your bundle of joy with Fragile X syndrome (FXS) is now bouncing off you, wide awake, screaming, smiling, and demanding you join the party before you all return to bed after a few rounds of cajoling and pleading. Minutes later, repeat, rinse. Hitting home? The oh-my-it’s-way-too-early morning parties may be over if new research by Cara Westmark, PhD, is successful. Westmark, senior scientist, Department of Neurology, University of Wisconsin previously found proteins involved in Alzheimer’s disease are over expressed in Fragile X mice. She believes drug treatments that normalize theRead more

Fragile X Treatment: New Research Directions

Fragile X Treatment: New Research Directions
Re-examining the Nature of Fragile X In the wake of negative results from several high-profile clinical trials in Fragile X, we find ourselves questioning many of our previous assumptions about the nature of this disorder. After all, understanding the basic pathology of disease is critical to development of new treatments — this is true across the board, in all branches of medicine. In the early days of Fragile X research, shortly after the FMR1 gene was discovered and the normal protein product of the gene (FMRP) was identified, it was noted that FMRP is an RNA binding protein. Whatever the normal function of this single protein which Fragile X patients lack, it had something to do with RNA metabolism. Since RNA is the template used to make new proteins, this meant that the Fragile X protein is involved in regulating protein synthesis. A synapse showing the axon of neuron 1,Read more

NIH Awards $35 Million to Three Fragile X Research Teams

NIH Awards $35 Million to Three Fragile X Research Teams
The National Institutes of Health has just announced new awards of $35 million over five years to support three Centers for Collaborative Research in Fragile X. Investigators at these centers will seek to better understand Fragile X-associated disorders and work toward developing effective treatments. All of these scientists have been funded for years by FRAXA Research Foundation, and now each team will receive over $2 million per year for five years! Kimberly M. Huber, Ph.D., University of Texas Southwestern Medical Center, Dallas (Grant number 1U54 HD082008-01) Many people with Fragile X syndrome are sensitive to sensory stimuli, especially noise. Dr. Huber’s team, along with Khaleel Razak, Ph.D., Iryna Ethell, Ph.D., and Devin Binder, Ph.D. of University of CA at Riverside, will study brain circuits in mouse models and people to try to determine the causes of heightened sensitivity to sound. This information may lead to more targeted therapies. Dr. HuberRead more

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Cellular-Specific Therapeutic Targeting of Inhibitory Circuits in Fragile X Syndrome

Studies have shown that the function of inhibitory networks is disturbed in Fragile X. This abnormality is not well understood but appears to be secondary to abnormalities in metabotropic glutamate and endocannabinoid systems. With a $90,000 grant from FRAXA in 2013-2014, Dr. Molly Huntsman’s team examined how these networks interact and how inhibitory deficits can best be remedied.

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Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists

Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists
With a $90,000 grant from the FRAXA Research Foundation, Dr. Robert Wong is investigating how seizures are generated in Fragile X neurons. More generally, he is looking at how synapses are modified to enable learning and memory and how this process is impaired in Fragile X. $90,000 Grant Robert Wong, PhD Principal Investigator State University of New York 2013-2014 FRAXA Research Grant $90,000 over 2 Years Abnormal increases in sensitivity of a type of glutamate receptor (group I mGluR) cause brain malfunction, including epilepsy, in Fragile X syndrome (FXS). We are examining a newly uncovered regulation of this increased group I mGluR sensitivity by a second type of glutamate receptor, the NMDA receptor. By looking at audiogenic seizures in FXS model mice, NMDA receptor blockers were found to robustly suppress these seizures at the young developmental stage. In contrast, the same antagonists activated seizure activities, normally dormant, in adult FXS model mice and in a CGGRead more

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

With a $66,000 grant from FRAXA Research Foundation in 2013, Dr. Lucia Ciranna and her team from the Universita di Catania tested if specific serotonins could reverse abnormal phentotypes found in Fragile X syndrome. 

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The Endocannabinoid System in a Mouse Model of Fragile X Syndrome

With a $128,500 grant over 2011-2013 from FRAXA Research Foundation, Drs. Bradley Alger and and Ai-Hui Tang at the University of Maryland researched endocannabinoid pathways in Fragile X.

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Using Fenobam to Reduce APP and Abeta in Fragile X Mice

Using Fenobam to Reduce APP and Abeta in Fragile X Mice

With a $130,000 grant from FRAXA Research Foundation over 2008-2008, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.

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Neurobiology of Fragile X Syndrome: A Unifying Neuro-Endocrine Hypothesis

With a $74,000 grant from FRAXA Research Foundation, Dr. Abdeslem El Idrissi at CUNY explored the GABA receptor system in Fragile X mice and tested somatostatin and taurine as potential therapies for Fragile X; while somatostatin must be infused intravenously, taurine is available as a nutritional supplement.

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Decreased Excitatory Drive onto Parvalbumin-Positive Neocortical Inhibitory Neurons in a Mouse Model of Fragile X Syndrome

Decreased Excitatory Drive onto Parvalbumin-Positive Neocortical Inhibitory Neurons in a Mouse Model of Fragile X Syndrome

With an $80,000 grant from FRAXA Research Foundation over 2006-7, Drs. Jay Gibson and Kimberly Huber at the University of Texas at Southwestern examined if the defected inhibitory neurotransmission was a primary or secondary symptom of Fragile X to determine where future treatment targets should be focused.

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The Molecular Basis of Increased Seizure Severity in the Fragile X Knockout Mouse

With a $50,000 grant from FRAXA Research Foundation from 2002-2003, Dr. Carl Dobkin and his team at the New York Institute for Basic Research studied the causes for heightened seizure activity in Fragile X mice. Results published.

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