With $375,000 in grants from the FRAXA Research Foundation since 2009, Dr. David Nelson has developed an impressive array of advanced mouse models of Fragile X, at Baylor College of Medicine. These models are available to investigators worldwide on request. This resource has been essential for a broad, rapid distribution of Fragile X and related gene mouse models and has increased the pace of Fragile X research.
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MicroRNAs as Biomarkers in Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation in 2015-2016, Dr. Mollie Meffert and Dr. Christina Timmerman at Johns Hopkins University studied groups of small RNAs, known as microRNAs, which are greatly decreased in brain tissue of Fragile X mice vs. normal controls.
Read moreRepurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome
With a $90,000 grant from the FRAXA Research Foundation, Dr. Lynne Maquat and Dr. Tatsuaki Kurosaki will investigate nonsense-mediated mRNA decay (NMD) in Fragile X. NMD is a “housekeeping” process that cells use to prevent faulty proteins from being made. But there is too much of it in Fragile X syndrome. There are already available drugs that suppress NMD – including caffeine.
Read moreKimberly Huber, PhD, Explores Hyperexcitability in Fragile X Syndrome
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.
Read moreAltered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target
With a $90,000 grant from FRAXA Research Foundation over 2016-2018, 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.
Read moreEnhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome
FRAXA Research Foundation funded a 2016-2017 Fellowship for Dr. Stephanie Barnes in the University of Edinburgh lab of Dr. Emily Osterweil. With this $90,000 award, the team is investigating NMDA signaling in fragile X syndrome mice.
Read moreBrain Revolution: French Scientists Bardoni and Maurin Study FMRP
Dr. Maurin and Dr. Bardoni were awarded $90,000 over two years from FRAXA Research Foundation for their project, “Modulating cAMP And cGMP Levels As A New Therapeutic Approach For FXS”, in May 2016. They aim to gain a better understanding of how the brain develops and functions Like snowflakes, people with Fragile X Syndrome are not all alike. Some respond differently to the same drugs, as previous Fragile X research has shown. Understanding this phenomena is leading French scientists Barbara Bardoni, PhD, and Thomas Maurin, PhD, to identify new drugs to improve treatments in patients with Fragile X.
Read moreUniversity of Michigan researcher Peter Todd, MD, PhD, Aims to Selectively Turn the Fragile X Gene Back on in Human Cells
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 brain development.
Read moreResearcher David Nelson, PhD, Explores New Cell Strategies for Fragile X Syndrome, FXTAS and FXPOI
It’s rare to find a researcher working on the Big Three — Fragile X Syndrome (FXS), Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) and Fragile X-associated primary ovarian insufficiency (FXPOI). Then again, David Nelson, PhD, is the rare bird. Nelson is a professor of Molecular and Human Genetics, Baylor College of Medicine, and director of Baylor’s Graduate Program in Integrative Molecular and Biomedical Sciences. He has been involved in FXS research since the late 1980s where he helped identify the mutation and the FMR1 gene. These days, researchers in Nelson’s lab at Baylor are studying FXS, FXTAS and FXPOI using mouse models.
Read moreDouble Down: Fragile X Clinical Trial Combines Two Available Drugs
If all the science world’s a stage, Fragile X researchers are more than merely players. They are center stage. So believes Francois Corbin, MD, PhD, professor, Université de Sherbrooke, Canada, who directs the university’s Fragile X Clinic. Corbin, who has received more than $100,000 in FRAXA support since 2012, is leading a pilot randomized Phase II trial, exploring the tolerability and the synergistic effect of a combined therapy.
Read moreThe X Factor – Turning on X Chromosome Genes to Treat X-linked Disorders
Harvard researcher Jeannie T. Lee, MD, PhD, moves closer to turning on select genes on the X chromosome to treat people with X-linked disorders.
Read moreFragile X Fruit Fly Research Bears Fruit
A new FRAXA-funded study shows how the hormone insulin – usually associated with diabetes — is involved in the daily activity patterns and learning deficits in the fruit fly model of Fragile X Syndrome (FXS). The study also reveal a metabolic pathway that can be targeted by new and already approved drugs to treat Fragile X patients, notably metformin.
Read moreAbnormalities of Synaptic Plasticity in the Fragile X Amygdala
With a $110,050 grant from FRAXA Research Foundation from 2005-2016, Dr. Sumantra Chattarji at the National Center for Biological Sciences researched how the amygdala is affected by Fragile X syndrome. Results published.
Read moreTargeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome
With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat Fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).
Read moreFruit Flies to Model and Test Fragile X Treatments
Dr. Jongens and his collaborators have found an insulin-like protein in the fly brain that is overexpressed in the Fragile X mutant fly, leading to increased activity of the insulin signaling pathway. Furthermore, they found that certain behavioral patterns in the Fragile X flies can be rescued by expressing the FX gene just in insulin producing neurons in the fly brain. In the mutant, there are other changes in the signaling pathways, including a decrease in cAMP and elevation in PI3K, mTOR, Akt and ERK activity. They now propose to study 2 medicines used for diabetes: pioglitazone (increases cAMP and decreases Akt and ERK) and metformin (inhibits mTOR), in flies and mice to validate the potential efficacy of these novel therapeutics for Fragile X.
Read moreAnalysis of Developmental Brain Dysfunction in Families
FRAXA Research Foundation is proud to make a grant of $90,000 over 2014-2015 to Margaret King, PhD. The goal of this project is to identify new approaches to clinical trial design for Fragile X pharmaceuticals.
Read moreFRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome
Mis-regulation of activity-dependent protein synthesis is one of the major cellular abnormalities found in Fragile X. Upstream neuronal signaling regulates a large cluster of enzymes called the mTORC1 complex, which in turn regulates protein synthesis. This complex is also controlled by cellular energy levels via the metabolic sensor AMP-activated Protein Kinase (AMPK). AMPK is a highly conserved kinase that is activated under conditions of energy stress, when intracellular ATP levels decline and intracellular AMP increases.
Read moreThe 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 Ai-Hui Tang at the University of Maryland researched endocannabinoid pathways in Fragile X.
Read moreInhibitors of STEP as a Novel Treatment of Fragile X Syndrome
With a $349,000 grant from FRAXA Research Foundation from 2008-2015, Dr. Paul Lombroso and his team at Yale University researched if inhibiting STEP could reduce behavioral abnormalities in Fragile X syndrome. Results published.
Read moreMolecular Mechanisms of Cytoskeletal Regulation by FMRP
With a 2-year, $120,000 grant from FRAXA Research Foundation in 2015, Dr. Samie Jaffrey from Weill Medical College of Cornell University will research the connection between FMR1, RhoA, and dendritic spine abnormalities.
Read moreTargeting the Endocannabinoid System in Adult Fragile X Mice
With a $90,000 grant from the FRAXA Research Foundation from 2013-2014, Dr. Andres Ozaita led a team to test rimonabant’s ability to blockade the CB1 receptor. Blocking CB1 has shown potential to reverse most symptoms of disease in mice bred to mimic Fragile X syndrome.
Read morePhase 1 Clinical Trial of Mega Green Tea Extract in Fragile X Syndrome
With a $124,000 grant from the FRAXA Research Foundation from 2012-2014, Dr. Mara Dierssen and Dr. Rafael de la Torre conducted preclinical studies in Fragile X knockout mice and a clinical trial in Fragile X patients using Mega Green Tea Extract, which contains 45% by weight epigallocatechin gallate (EGCG).
Read moreFunctional Interplay Between FMRP and CDK5 Signaling
With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the Fragile X protein, FMRP, in the Fragile X mouse model.
Read moreComputational Analysis of Neural Circuit Disruption in Fragile X Model Mice
Computer modeling of the brain offers the hope of predicting how the brain responds to varying conditions, but these models have been rather primitive until recently. The Sejnowski team at the Salk Institute, who specialize in computational models of neural networks, will take the results of previous FRAXA-funded projects and incorporate them into their advanced computer models of brain function.
Read moreSynaptic Characterization of Human Fragile X Neurons
With a $90,000 grant from FRAXA Research Foundation over 2013-14, Dr. Marius Wernig and Dr. Samuele Marro at Stanford analyzed homeostatic plasticity and regulation of synaptic strength by retinoic acid. If the results are encouraging, they will move forward with testing whether available RA antagonists can alleviate observed abnormalities in these cells.
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