FRAXA Research Foundation has awarded a $90,000 grant to Principal Investigator Dr. Sean McBride and Postdoctoral Fellow Dr. Karen Joyce, at Rowan University, to screen all 2,320 FDA-approved drugs on both mouse and fly models of Fragile X syndrome. Those drugs which show promise will be tested in more detail for potential to treat Fragile X in humans.
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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.
Read moreCoffee, Tea, and Chocolate: Adenosine Receptors in Fragile X
Caffeine is the most popular smart drug in the world. With a $90,000 grant from FRAXA Research Foundation, Alberto Martire, PhD and Antonella Borreca, PhD in Rome, Italy are investigating adenosine receptors antagonists to treat Fragile X syndrome. Compounds which are able to block adenosine receptors are commonly found in tea, chocolate, and coffee.
Read moreFinding Fragile X Biomarkers – From Transcriptomics to Behavior in Patients
With this $20,000 award from FRAXA Research Foundation, Dr. Vanderklish and collaborators at Scripps Research Institute, the University of Chile, and the FLENI Institute in Argentina are analyzing patterns in gene expression in blood cells of patients with Fragile X syndrome. They are using “transcriptomics” which can produce a time-sensitive signature of an individual person. This is the first time that all these different levels of study – from transcriptomics to behavior – have been done for individual patients with Fragile X.
Read moreResearch Points to Drugs which Inhibit PDE to Treat Fragile X
FRAXA Research Foundation funded a grant of $90,000 over 2016-2018, for a postdoctoral fellowship for Thomas Maurin, PhD, working under the mentorship of Dr. Barbara Bardoni at INSERM in France. The team works on the biochemistry of the Fragile X protein. They have found that PDE inhibitors (a class of drugs) show promise as treatments for Fragile X syndrome. In related research, FRAXA is currently funding a clinical trial of PDE4D inhibitors.
Read moreMetformin and Aberrant Insulin Signaling in a Fragile X Mouse Model
This 2017-2018 grant of $90,000 is funded jointly by FRAXA and the Fragile X Research Foundation of Canada for the first year. A previous FRAXA grant to the Sonenberg lab has led to great interest in the available drug, metformin, as a potential treatment for Fragile X syndrome. FRAXA is currently organizing clinical trials of metformin.
Read moreNKCC1 Inhibitor Bumetanide Corrects Synaptic and Circuit Hyperexcitability in Fragile X Mouse Model
With $258,000 in grants since 2013 from FRAXA Research Foundation, Dr. Anis Contractor and Dr. Qionger He at Northwestern University are exploring the potential of the available drug bumetanide to correct altered GABA signalling in a mouse model of Fragile X syndrome.
Read moreNon-Invasive Imaging as a Biomarker for Fragile X Clinical Trials
FRAXA Research Foundation has renewed Kamila Castro’s 2017 FRAXA Fellowship for a second year. With this $90,000 award, Kamila Castro and Principal Investigator Dr. Andreas Frick are using non-invasive magnetic resonance imaging (MRI) methodology to assess connectivity changes in the brain in Fragile X. If this project is successful, we will have objective outcome measures to evaluate new treatments, both in mice bred to mimic Fragile X and in human patients.
Read moreActivity-Dependent Translational Profiling in Fragile X Neurons
FRAXA’s first-ever grant to researchers at the University of California at Berkeley goes to Dr. Nicholas Ingolia and Dr. J. Wren Kim to analyze the proteomics of Fragile X neurons using a newly developed tool which can distinguish the profiles of neurons that are actively responding to signals.
Read moreTetra Discovery Partners Initiates Phase 2 Trial of BPN14770 in Fragile X Syndrome
This 2-Period Crossover Study of BPN14770 is accepting adults males with Fragile X syndrome at Rush University Medical Center in Chicago. Principal Investigator of the study is Elizabeth Berry-Kravis, MD, PhD.
A selective inhibitor of the phosphodiesterase type-4D (PDE4D), BPN14770 has shown the ability to improve the quality of connections between neurons and to improve multiple behavioral outcomes in the Fragile X mouse model.
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.
Read moreThree-Dimensional Model for Identifying Fragile X Treatments
With a $90,000 grant from FRAXA Research Foundation awarded in 2018, Dr. Peng Jin and Dr. Juhnee Kang at Emory University will develop and analyze Fragile X brain organoids to understand the disorder and identify treatment targets.
Read morePharmacological Tolerance in the Treatment of Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation over 2018-2019, Dr. Patrick McCamphill, postdoctoral fellow in Dr. Mark Bear’s lab at Massachusetts Institute of Technology (MIT), is investigating drug tolerance to mGluR5 antagonists, arbaclofen, and other potential Fragile X treatments. He is also exploring ways to overcome it.
Read moreFragile X Clinical Trial of AZD7325 in Adults
With a $51,000 grant from FRAXA Research Foundation, Dr. Craig Erickson conducting a double-blind, placebo-controlled clinical trial of AZD7325 in adults ages 18-50 with Fragile X syndrome at Cincinnati Children’s Hospital. The compound being studied is an investigational new drug from AstraZeneca that targets GABA (A) receptors.
Read moreCRISPR Reactivation of the Fragile X Gene
“We are trying to target the first event that goes wrong in Fragile X syndrome”, says Todd, “One reason our previous attempts to develop treatments for Fragile X syndrome have failed is that they’ve tried to target the downstream effects of losing the Fragile X protein. The protein does many things… bypassing all the functions that it normally takes care of has proven difficult from a pharmacologic perspective.”
Read moreIn 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, with brief updates from researchers investigating Fragile X.
Read moreBrain Imbalance Target of Dr. Erickson’s New Clinical Trial
According to Dr. Erickson, AZD7325 is a drug that selectively boosts GABA neurotransmission in the brain. GABA is the primary neurochemical in the brain that blocks brain activation. GABA activity is in balance in the brain with Glutamate activity, which is the primary neurochemical that causes brain activation. In Fragile X, GABA activity is insufficient and glutamate activity is excessive, likely causing brain activity to be out of balance. AZD7325 attempts to correct parts of this imbalance by boosting the insufficient GABA activity in the brains of people with Fragile X.
Read moreCombinatorial 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.
Read moreMicroRNA Mediated Astroglial GLT1 Dysregulation in Fragile X
Almost all brain research focuses on neurons – nerve cells. However, the brain has many more glial cells which support, nourish, and protect the neurons. FRAXA Research Foundation awarded a 2017 grant $90,000 to support Dr. Yang’s studies of how changes in glial cells contribute to Fragile X syndrome. This grant is funded by a grant from the Pierce Family Fragile X Foundation.
Read moreAutophagy is a Novel Therapeutic Target of Impaired Cognition in Fragile X Syndrome
Dr. Suzanne Zukin, at Albert Einstein College of Medicine, is expert on signaling pathways in the brain and the regulation of synaptic plasticity. With this 2017 grant of $90,000 from FRAXA Research Foundation, she and her team are exploring autophagy, which is how cells clean house, in Fragile X.
Read moreQuantitative Assessment of the Serotonin System in a Mouse Model of Fragile X Syndrome
FRAXA Research Foundation awarded a grant of $90,000 over two years to Clinton Canal, PhD. Dr. Canal, previously a research assistant professor at Northeastern University, has just launched his own lab at Mercer University in Atlanta, GA, to focus on Fragile X research.
Read moreTargeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells
With a $90,000 grant from FRAXA Research Foundation awarded in 2016, University of Michigan researcher Peter Todd, MD, PhD, is using CRISPR to selectively turn the Fragile X gene back on in stem cells.
Read moreDefining Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists
With $217,500 in grants from FRAXA Research Foundation, Dr. Karen O’Malley and team studied the function of mGluR5 when it is inside cells. Many of the symptoms of Fragile X Syndrome (FXS) are thought to arise due to overactive metabotropic glutamate receptor 5 (mGluR5) signaling, which is normally opposed by the protein missing in FXS, Fragile X Protein (FMRP).
Read moreInvestigating Gene Reactivation to Treat Fragile X Syndrome
With a $180,000 grant from FRAXA Research Foundation from 2016-2017, Dr. Jeannie Lee and her team at Harvard are working to reactivate the gene that is silenced in Fragile X syndrome.
Read moreMechanisms of Tolerance to Chronic mGluR5 Inhibition
Over the past few years, both Novartis and Roche sponsored large-scale clinical trials of metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) to treat Fragile X syndrome (FXS). With a $90,000 grant from FRAXA Research Foundation in 2015-2017, Dr. Mark Bear’s team will explore if mGlu5 NAMs dosed chronically causes tolerance, and if so, how it develops and to probe new avenues to prevent or circumvent it.
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