Recruiting: Clinical Study of Non-Invasive EEG for Children Ages 2-7

Recruiting: Clinical Study of Non-Invasive EEG for Children Ages 2-7

Dr. Carol Wilkinson, MD PhD, and Dr. Charles Nelson, PhD, at Boston Children’s Hospital are recruiting children ages 2-7 years with Fragile X syndrome to join a study of brain differences using non-invasive EEG.

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Novel Modulators of Potassium Channels to Treat Fragile X

Novel Modulators of Potassium Channels to Treat Fragile X

With funding from FRAXA over 2015-2017, the Yale University team of Leonard Kaczmarek, PhD showed that the firing patterns of auditory neurons in response to repeated stimulation is severely abnormal in Fragile X mice. Based on these results, they are collaborating with the UK-based company Autifony to develop advanced compounds which may reverse these deficits.

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Lucas Turned 21, Yet Not Much has Changed – Clark Family Campaign

Lucas Turned 21, Yet Not Much has Changed – Clark Family Campaign

Lucas turned 21 this year, a fun milestone for most young adults, but not as eventful for someone with Fragile X syndrome. Lucas still prefers isolation in his room, fast-forwarding and rewinding to his favorite spots in his DVD collection, doing the same for videos on the internet, and his favorite internet pastime: shopping for die-cast toy cars and trucks.

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Understanding and Reversing Hypersensitivity to Sounds in Fragile X Syndrome

Understanding and Reversing Hypersensitivity to Sounds in Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation over 2018-2019, Drs. Devin Binder, Iryna Ethell, and Patricia Pirbhoy at the University of California at Riverside aim to understand – and reverse – hypersensitivity to sound in Fragile X syndrome.

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Auditory Dysfunction in Fragile X Syndrome, Role for the Sound Localization Pathway

Auditory Dysfunction in Fragile X Syndrome, Role for the Sound Localization Pathway

FRAXA Research Foundation has renewed Dr. Elizabeth McCullagh’s 2017 FRAXA Fellowship for a second year. Dr. McCullagh and Principal Investigator Dr. Achem Klug are investigating the “cocktail party effect” in Fragile X mice. There is a specific circuit which allows us to discriminate between competing sound sources, helping us focus on a sound source of interest such as with a conversation partner. If clear differences are found in this circuit, they could be used as potential biomarkers for Fragile X clinical trials.

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FRAXA Research Grants Drive Big Investments in Fragile X

FRAXA Research Grants Drive Big Investments in Fragile X

Most people know that FRAXA supports academic research at many institutions such as Harvard University, University of Pennsylvania, Massachusetts Institute of Technology, and Yale University. However, FRAXA is also working with more than 30 pharmaceutical companies around the world. Mike spends a lot of his time advising and collaborating with industry partners.

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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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Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers

Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers

With a $90,000 grant from FRAXA Research Foundation awarded over 2016-2017, University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, are exploring drug combinations to limit hypersensitivity to sounds in Fragile X mice.  

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Neural Markers of Fragile X: A Powerful New Tool for Clinical Trials

Neural Markers of Fragile X: A Powerful New Tool for Clinical Trials

Once the neural marker is identified for a particular challenge, such as kids with poor language versus good language, neural markers can be measured during drug and behavioral therapy trials to see if a child is improving based on objective biological measures.

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Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

FRAXA Research Foundation awarded $122,000 over 2016-2018 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.

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Kimberly Huber, PhD, Explores Hyperexcitability in Fragile X Syndrome

Kimberly Huber, PhD, Explores Hyperexcitability in Fragile X Syndrome
Sensory Overload Ever wonder why your child with Fragile X suddenly screams for no apparent reason or jumps and flaps uncontrollably seemingly for hours? You got it: hyperexcitability. But what exactly causes it? And what can fix it? Kimberly Huber, PhD, is working long and hard in her lab to answer those questions. Dr. Huber, professor, Neuroscience, UT Southwestern Medical Center, is seeking to understand how FMRP regulates connections between brain cells, called synapses, and the function of brain circuits, which are several connected brain cells. Her current focus is the study of synapses and brain circuits in the mouse that mediate sensory perception, including perception of touch and sound. She aims to understand the cellular and molecular mechanisms by which loss of FMRP causes hyperexcitable sensory circuits. The goal: to develop targeted therapeutics that can restore normal brain function and reduce sensory hypersensitivity. “Sensory brain circuits are overactive, or hyperexcitable,Read more

University of Michigan researcher Peter Todd, MD, PhD, Aims to Selectively Turn the Fragile X Gene Back on in Human Cells

University of Michigan researcher Peter Todd, MD, PhD, Aims to Selectively Turn the Fragile X Gene Back on in Human Cells
Targeted transcriptional reactivation of FMR1 in Fragile X Syndrome stem cells Peter Todd MD, PhD Principal Investigator Jill Haenfler PhD Postdoctoral Fellow University of Michigan Medical Center $45,000 in 2016 renewed for $45,000 in 2017 Swimming Upstream Fish like salmon are born in fresh water streams and rivers. When the time comes for them to breed, they return to the stream of their birth to lay eggs in the same spot where they were born. To accomplish this, they must swim upstream against the current or flow of the stream. Taking a page out of the salmon DNA playbook, University of Michigan scientists Peter Todd, MD, PhD, and postdoctoral fellow Jill Haenfler, Ph.D., are exploring unchartered waters to find a cure for Fragile X Syndrome. The researchers are adapting CRISPR research to reactivate the FMR1 gene, which provides instructions for making a protein called FMRP — needed for normal brainRead more

Meltdown no more? Targeting Hypersensitivity in Fragile X

Meltdown no more? Targeting Hypersensitivity in Fragile X
University of California Researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, Explore Drug Combinations to Limit Hypersensitivity to Sounds in Fragile X Mice We’ve all been there. Our child with Fragile X hears something and becomes excited. Very excited. Hand flapping follows with non-stop jumping and ear-piercing squawking. Nothing helps. No meds. No iPhone. No magic toy. Several minutes go by. Sometimes longer. How many times have you apologized in a grocery store — or restaurant — or at the mall? Wouldn’t it make our lives better if this unpredictable excitability was minimalized or eliminated? That’s the premise behind research being conducted at University of California, Riverside. Principal Investigator Khaleel Razak, PhD, and postdoctoral fellow Jonathan W. Lovelace, PhD, are studying mice genetically altered to mimic the genetic characteristics of humans with Fragile X Syndrome. Their focus is on the mouse brain’s electrical activity when different kinds of soundsRead 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

Potassium Channel Modulators to Treat Fragile X

Potassium Channel Modulators to Treat Fragile X

With $246,000 in funding from FRAXA over 2012-2014, the Yale University team of Leonard Kaczmarek, PhD, showed that loss of FMRP leads to an increased Kv3.1 potassium currents and decreased Slack potassium currents in neurons. Both of these changes impair timing of action potentials in auditory neurons (and likely others throughout the brain). The team also found that the firing pattern of neurons in response to repeated stimulation is severely abnormal in Fragile X mice. Based on these results, they are collaborating with the UK-based company Autifony to develop and test advanced compounds which may reverse these deficits.

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Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

With $135,000 in grants from FRAXA Research Foundation over several years, Dr. Khaleel Razak and Dr. Iryna Ethell explored robust biomarkers relevant to the FXS and the efficacy of minocycline treatment.

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Compound that Inhibits mGluR5 Corrects Signs of Fragile X in Adult Mice

A study finds that a new compound reverses many of the major symptoms associated with Fragile X syndrome (FXS). The paper is published in the April 12 issue of the journal Neuron, describes the exciting observation that the FXS correction can occur in adult mice, after the symptoms of the condition have already been established. Previous research has suggested that inhibition of mGlu5, a subtype of receptor for the excitatory neurotransmitter glutamate, may ameliorate many of the major symptoms of the disease. This study, a collaboration between a group at Roche in Switzerland, led by Dr. Lothar Lindemann, and Dr. Mark Bear’s MIT lab, used an mGlu5 inhibitor called CTEP to examine whether inhibition of mGlu5 could reverse FXS symptoms. The researchers gave CTEP to mice which model Fragile X. "We found that even when treatment with CTEP was started in adult mice, it reduced a wide range of FXSRead more

The Slack Potassium Ion channel as a Therapeutic Target for Fragile X Syndrome

A paper on this work has been published in Journal of Neuroscience on 2010 August 4: Fragile X mental retardation protein is required for rapid experience-dependent regulation of the potassium channel Kv3.1b by Leonard Kaczmarek, PhD and Jack Kronengold, PhD Our laboratory has investigated how the excitability of neurons becomes modified in the absence of the FMRP protein. We have found that the levels of two potassium channels, termed Slack and Kv3.1 are altered in mice that lack this protein. We have made significant progress in identifying novel pharmacological activators of the Slack potassium channel for potential therapeutic intervention in FXS individuals. The Slack potassium channel is widely expressed in the brain. Using neurons of the central auditory system, our laboratory has demonstrated that Slack is required for accurate timing of action potentials in response to synaptic stimuli. This channel is activated by the FMRP protein through a direct association

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GABAergic Inhibitory Function in Fragile X Syndrome

GABAergic Inhibitory Function in Fragile X Syndrome

With a $100,000 grant from FRAXA Research Foundation, Drs. Joshua Corbin and Molly Huntsman from the Children’s National Medical Center examined the role of a particular class of brain cells (inhibitory interneurons) that dampen excessive activity in the “emotional center of the brain” (the amydala). This inhibition is deficient in Fragile X, and so they are looked for ways to remedy this. This is particularly interesting to parents of children who are overly anxious and emotional. They worked with Dr. Walter Kaufmann, a clinician at Kennedy Krieger Institute in Maryland.

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Genome-wide Epigenetic Markers in Fragile X

Genome-wide Epigenetic Markers in Fragile X

With $45,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth of Cornell University studied epigenetics (ie factors other than the gene itself) which can determine symptom severity in Fragile X.

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Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse

Electrophysiological, Biochemical and Immunohistochemical Characterization of Kv3.1 in Auditory Brainstem Nuclei in the Fragile X Knockout Mouse

With $80,000 in funding from FRAXA over several years, the Yale University team of Leonard Kaczmarek, PhD showed that loss of FMRP leads to an increased Kv3.1 potassium currents. This change impairs timing of action potentials in auditory neurons (and likely others throughout the brain).

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Baclofen: GABA(B) Receptor Supersensitivity and Normalization of Behavioral Abnormalities by Various GABA(B) Agonists Including Baclofen in FMRP Deficient Mice

Baclofen: GABA(B) Receptor Supersensitivity and Normalization of Behavioral Abnormalities by Various GABA(B) Agonists Including Baclofen in FMRP Deficient Mice

With $110,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth from Cornell University discovered increased startle response in Fragile X mice and that baclofen can correct this phenotype.

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Genetic and Behavioral Analyses of the dFMR1 Pathway in Drosophila Peripheral Nervous System

Genetic and Behavioral Analyses of the dFMR1 Pathway in Drosophila Peripheral Nervous System

With a $160,000 grant from FRAXA Research Foundation from 2004-2006, Dr. Fen-Biao Gao and his team at the University of California studied the relationship between mRNA and FMRP.

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