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.
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Students at WPI helping FRAXA Research Foundation
Undergraduate students at Worcester Polytechnic Institute (WPI) complete what is known as the Interactive Qualifying Project (IQP). Student groups work closely with local or national sponsors during their junior year to complete a project that benefits their community. Two student groups from WPI are working with FRAXA to provide research-based improvements to the FRAXA.org website, and to develop a mobile FRAXA app.
Read moreNPR, “A Family’s Long Search For Fragile X Drug Finds Frustration, Hope”
There is no effective treatment for the rare genetic disorder Fragile X syndrome, so two parents created a foundation to fund research. But they found there’s no easy road to a cure. For a few weeks last year, Michael Tranfaglia and Katie Clapp saw a remarkable change in their son, Andy…
Read moreNIH 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!
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.
Read moreBcl-xL Inhibition as a Therapeutic Strategy for Fragile X Syndrome
Scientists have found increases in the numbers of neurons in brain regions of autistic children, suggesting a problem in developmental programmed cell death pathways. One of the most important effectors of neuronal survival during brain development is the “anti-cell death” protein Bcl-xL. While the normal function of Bcl-xL is to maintain a healthy number of neurons and synapses, over-expressed Bcl-xL can cause an overabundance of synaptic connections. This may be happening in Fragile X.
Read moreSeizures 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.
Read moreNovartis Discontinues Development of mavoglurant (AFQ056) for Fragile X Syndrome
Novartis has announced that the company will be discontinuing its development program in Fragile X for its lead mGluR5 antagonist, mavoglurant (AFQ056), following negative results in a large international clinical trial in adults (reported in the Fall of 2013) and most recently, in a trial in adolescents. In both placebo-controlled trials, patients taking mavoglurant did not show improvement over placebo in any outcome measures. Novartis has also announced that the current open-label extension phase of the trial will be closed, but patients will be allowed to continue on the medication until their next scheduled clinic visit, or August 29, whichever comes first.
Read moreNew Clue to Fragile X and Autism Found Inside Brain Cells
Researchers led by Dr. Karen O’Malley at Washington University School of Medicine in St. Louis have published results of their work on mGluR5 and Fragile X syndrome. FRAXA Research Foundation provided funding for this work from 2009 until 2013. Pharmaceutical companies have developed therapeutic compounds to decrease signaling associated with the mGlu5 receptor, moderating its effects on brain cells’ volume knobs. But the compounds were designed to target mGlu5 surface receptors. In light of the new findings, the scientists question if those drugs will reach the receptors inside cells.
Read moreScientists Uncover Trigger for Fragile X Syndrome
A new study led by Weill Cornell Medical College scientists shows that Fragile X syndrome occurs because of a mechanism that shuts off the gene associated with the disease. The findings, published today in Science, also show that a compound that blocks this silencing mechanism can prevent Fragile X syndrome – suggesting a similar therapy may be possible for 20 other diseases that range from mental retardation to multisystem failure.
Read moreSmall Molecules To Target r(CGG) Expansions to Treat Fragile X Syndrome
With a 2-year, $90,000 grant from FRAXA Research Foundation, Dr.’s Matthew Disney and Wang-Yong Yang worked to correct the underlying problem in Fragile X: the silencing of the Fragile X gene (FMR1) and the resulting lack of FMRP (Fragile X Mental Retardation Protein). Their approach was to use novel small molecules to target the abnormal CGG repeats before the FMR1 gene.
Read morePotassium 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.
Read moreMolecular mechanisms: Enzyme blockers help Fragile X mice
Dr. Jope won the 2013 FRAXA Pioneer Award for this work. The mood stabilizer lithium and two other drugs that block an enzyme called GSK-3 reverse cognitive deficits in a mouse model of Fragile X.
Read moreThis Is My Brother, speech by Elizabeth Clark at FRAXA’s Fall X Ball
In a heartfelt, humorous and insightful speech, Elizabeth Higgins Clark imparts the inspiration and love she has received from her brother, David, who has Fragile X Syndrome. Fragile X is the most common form of genetically transferred intellectual disability. Clark gave the following speech in Danbury, Connecticut at the 11th Annual Fall X Ball benefitting the FRAXA Research Foundation.
Read moreFragile X Syndrome Protein Linked to Breast Cancer Progression
Claudia Bagni (VIB/KU Leuven, Belgium, and the University of Rome, Italy) and colleagues have identified the way Fragile X Mental Retardation Protein or FMRP contributes to the progression of breast cancer. The researchers demonstrated that FMRP acts as a master switch controlling the levels of several proteins involved in different stages of aggressive breast cancer, including the invasion of cancer cells into blood vessels and the spread of these cancer cells to other tissues forming metastasis.
Read moreSocial Behavior as an Outcome Measure for Fragile X Clinical Trials
One of the features of the Fragile X mouse model which is relevant to the human Fragile X syndrome (and autism) is social behavior. Several tests show consistent social behavioral abnormalities in the Fragile X mouse model. With a $140,000 grant from FRAXA Research Foundation in 2012-2013, Dr. Willemsen at Erasmus University used social behavior tests to measure the effectiveness of several drug strategies.
Read moreTranslation-Independent Functions of FMRP in Excitability, Synaptic Transmission and Plasticity
With a $140,000 grant from FRAXA Research Foundation, Dr. Vitaly Klyachko and team at Washington University explored STP (short-term plasticity) in Fragile X, namely looking at presynaptic calcium dynamics as a major underlying cause of the STP defects.
Read moreGlycogen Synthase Kinase-3 (GSK3), Lithium and Fragile X
With $208,000 in funds from FRAXA Research Foundation, Dr. Richard Jope and his team at the University of Miami tested whether newly developed, highly specific inhibitors of GSK3 can reduce behavioral abnormalities in Fragile X mice.
Read moreDevelopment of a Novel GABA-A Agonist in Fragile X Syndrome
Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in Fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional paradoxical agitation, which limits their use.
Read moreThe mTOR Pathway in Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation over 2012-2013, Dr. Eric Klann and Postdoctoral Fellow Dr. Aditi Bhattacharrya of New York University investigated alterations in the mTOR pathway in Fragile X syndrome – which is also known to be defective in several forms of autism. Their work was published in September 2012 and received international attention.
Read moreMatrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome
With a $157,000 grant from the FRAXA Research Foundation in 2012-2013, Dr. Kendal Broadie and Dr. Cheryl Gatto worked to define the distinct but also overlapping roles for MMP-1 and MMP-2 in synaptic structural and functional development. In drug studies with Fragile X fruit flies, they will be testing a range of MMPIs in drug treatments to compare effectiveness during development and at maturity, in order to define the contributions of FXS developmental impairments and adult recovery/plasticity.
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