Callum Cup 2017 Raised over $9200 for Fragile X Research

We are tremendously grateful to the Millburn United men's soccer team, of Millburn, New Jersey, who held the 2017 Callum Cup on Sunday, July 2, 2017. They were honoring Callum Murphy, son of the team goalkeeper at Millburn United. Together with their friends and families, the team raised over $9000 for fragile X research! This event was made possibly by co-hosts Andrew Murphy and Nick Dawes. Thank you all! Donors -- Thank you all so much! Kathleen Warnock Sean Mahoney Daniel Losik Martin Leys Alexia Bucciarelli James Padykula Margaret Fox Beth Hopkins James Bayne Eva Lesiak Scott Heiman Brian Levine Vlad Sali Jean-Luc DeguinesRead more

Biomarker Discovery and Validation for Fragile X Syndrome

With a $60,000 grant from FRAXA Research Foundation in 2015 that was renewed in 2016, Dr. Eric Klann of New York University will research biomarkers in fraile X syndrome and how to translate these markers from mouse models to human patients.

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Function of FMRP and Test of a Novel Therapeutic Approach in a Fragile X Mouse Model

Function of FMRP and Test of a Novel Therapeutic Approach in a Fragile X Mouse Model

With a 2015-2016 $90,000 grant from FRAXA Research Foundation, Dr. Herve Moine and Dr. Andrea Geoffroy aim to uncover the exact role of FMRP and to test a novel possible means to correct for FMRP absence in the mouse model of fragile X syndrome.

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Correcting Defects in Astrocyte Signaling in Fragile X Syndrome

Correcting Defects in Astrocyte Signaling in Fragile X Syndrome

With a $90,000 grant from the FRAXA Research Foundation from 2015-2016, Dr. Laurie Doering and Dr. Angela Scott at McMasters University studied astrocytes in fragile X. Astrocytes, brain cells which support neurons, do not transmit signals. Several treatment strategies for fragile X have been proposed based on correction of “astrocyte phenotypes”.

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Sensory Hypersensibility in Fragile X Syndrome and BK Channel Openers

Sensory Hypersensibility in Fragile X Syndrome and BK Channel Openers

With $366,100 in grants from FRAXA Research Foundation, these investigators at the University of Orleans studied sensory abnormalities in fragile X mice and test the ability of a class of drugs, BK channel openers, to rescue these abnormalities.

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Fragile X Mutant Mouse Facility

Fragile X Mutant Mouse Facility

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

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.

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Repurposing Drugs to Dampen Hyperactive Nonsense-Mediated Decay in Fragile X Syndrome

Repurposing 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.

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Fulcrum Therapeutics Launched with $55 Million to Reactivate the Fragile X Gene

Fulcrum Therapeutics Launched with $55 Million to Reactivate the Fragile X Gene

A new company has launched that will invest tens of millions in reactivating the fragile X gene. With $55 million in investment funds, Fulcrum Therapeutics in Cambridge, MA, aim to develop small molecules to control gene expression. These potential new treatments would be based on controlling genetic on- and off-switches of disease genes. Fulcrum will start with two diseases: fragile X syndrome and a rare form of muscular dystrophy. FRAXA is funding one of the founding scientists, Jeannie Lee, MD, PhD, of Harvard University, and has been working with others on the new Fulcrum team. In fact, Dr. Lee will be our speaker at the FRAXA Fall Fling fundraiser this September 30, in Cambridge, Mass. Together, with your support and with support from new companies like Fulcrum, with support from FRAXA’s Nobel Laureate-laden Scientific Advisory Board and passionate Board of Directors, we are united more than ever in finding a cure for fragile

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New compound from Anavex improves learning and behavior in Fragile X mice

New compound from Anavex improves learning and behavior in Fragile X mice

A potential new treatment for Fragile X syndrome is showing promise. While still early in development, the investigational drug was able to improve intellectual, learning and hyperactivity measures in a mouse model of Fragile X syndrome. Anavex 2-73 is a sigma-1 receptor agonist being developed for autism spectrum disorders, including Rett syndrome and Fragile X syndrome, and for Alzheimer’s disease. Anavex Life Sciences presented the data at the Gordon Research Conference for Fragile X and Autism-Related Disorders, held June 5-10, 2016 in Mount Snow, VT. The study was sponsored by FRAXA, via the FRAXA Drug Validation Initiative, and performed by Fraunhofer Chile Research, in Santiago, Chile. “The ANAVEX 2-73 data in an array of behavioral paradigms in a validated mouse model of Fragile X is very encouraging. The results are promising for both Fragile X syndrome and Autism Spectrum Disorders, since there is an overlap in the clinical as well as

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Fragile X Fruit Fly Research Bears Fruit

Fragile X Fruit Fly Research Bears Fruit

Study on Fragile X Syndrome Uses Fruit Fly’s Point of View to Identify New Treatment Paths Adapted from press release by University of Pennsylvania 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. The scientists study the common fruitfly, Drosophila, whose genome contains a cousin, or homologue, of the human FMR1 gene called dfmr1. The lab of Thomas Jongens, PhD, an associate professor of Genetics, along with doctoral student Rachel Monyak and Sean McBride, MD, PhD, a psychiatrist at the Adult Developmental Disorders and Monogenic Disorders Clinic with Penn Behavioral Health, have been working with the fly model to find new therapies to

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Abnormalities of Synaptic Plasticity in the Fragile X Amygdala

Abnormalities 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.

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FRAXA Grants and Fellowships for Fragile X Research – 2016 Funding Priorities

FRAXA Grants and Fellowships for Fragile X Research – 2016 Funding Priorities

2016 Funding Priorities start with Clinical Trials While FRAXA Research Foundation’s research goals remain largely unchanged, the landscape in which we operate has changed significantly in the past few years.  Negative results from the major clinical trials of investigational agents have resulted in cessation of development of mGluR5 antagonists for fragile X syndrome.  There is still much evidence that this drug class could be successful as a fragile X therapeutic, but we do not see the need for more “proof of principle”-type preclinical research on mGluR5 antagonists. Studies of possible mechanisms of tolerance in fragile X would be appealing as a topic going forward, as would studies of circuit function in fragile X, since available evidence suggests some form of circuit-based (rather than synaptic) tolerance in fragile X mice and humans. Other potential areas of interest would include exploration of combination treatment strategies, both in animal models and in clinical trials. 

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Neuren’s trofinetide successful in Phase 2 clinical trial in Fragile X

Neuren’s trofinetide successful in Phase 2 clinical trial in Fragile X

We are pleased to share great news adapted from Neuren’s press release: Neuren’s phase 2 trial has successfully established proof of concept and provides a strong rationale for Neuren to move forward with developing trofinetide for Fragile X syndrome. In this initial small trial with a relatively short treatment period, trofinetide was very well tolerated, with the high dose (70 mg/kg twice daily) demonstrating a consistent pattern of clinical improvement, observed in both clinician and caregiver assessments. After only 28 days of treatment, improvements were seen across core symptoms of Fragile X syndrome, including higher sensory tolerance, reduced anxiety, better self-regulation and more social engagement. No serious adverse events were reported. Positive Results in Fragile X Syndrome and Rett Syndrome Beneficial effects of trofinetide have now been observed in both Fragile X syndrome and Rett syndrome. Neuren announced encouraging results of their phase 2 trofinetide trial in Rett Syndrome last year. Trofinetide Tested at FRAXA’s Drug Validation

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Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

Targeting 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).

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Fruit Flies to Model and Test Fragile X Treatments

Fruit 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.

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FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

FRAXA Grant to Nahum Sonenberg, PhD — Effects of metformin in Fmr1 knockout mouse model of Fragile X syndrome

2015 Program Grant funded for $100,000 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.  AMPK normally mediates mTORC1 suppression, but AMPK appears to be decreased in fragile X. Metformin, an FDA-approved drug, is widely used as a first-line therapy for type 2, and is a well known activator of AMPK.  It controls gene expression at the level of mRNA translation, comparable to the mTORC1 inhibitor rapamycin. This project will explore the potential of metformin and related compounds to rescue known abnormalities in fragile

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Bryostatin Restores Learning and Memory in Adult Fragile X Mice

Bryostatin Restores Learning and Memory in Adult Fragile X Mice
Just as the Amazon rainforest may hold a cure for cancer if only scientists can find it, a bizarre marine critter found off the California coast — Bugula neritina— is the only known source of a potential new Fragile X treatment, Bryostatin. Last month, FRAXA sat down with scientists from Neurotrope BioScience, a specialty biopharmaceutical company developing medicines for rare diseases and Alzheimer’s based on Bryostatin. Their Fragile X program is based on research by a West Virginia team led by Daniel Alkon, MD, which showed that Bryostatin-1 restores hippocampal synapses and spatial learning and memory in adult fragile X mice. “Our results show that synaptic and cognitive function of adult FXS mice can be normalized through pharmacologic treatment and that bryostatin-1-like agents may represent a novel class of drugs to treat fragile X mental retardation even after postpartum brain development has largely completed,” remarked Dr. Alkon. Bugula neritina, the source of bryostatin. Photo source http://seanet.stanford.edu/Bryozoa/ Bugula and Bryostatins Often mistakenRead more

Fragile X Programs at UMASS – University of MA, Worcester

Fragile X Programs at UMASS – University of MA, Worcester

Fragile X Programs aimed at improving the lives of individuals with Fragile X Syndrome at UMASS Medical School (UMMS) and UMASS Memorial Health Care (UMMHC) 1. Fragile X Syndrome Behavioral Health Clinic The Center for Autism and Neurodevelopmental Disorders (CANDO) is opening a specialty clinic for individuals with Fragile X Syndrome (under the direction of Dr. Jean Frazier) to evaluate and provide treatment for behavioral challenges. If you have questions about our program and/or have a need for our new clinical service, please call CANDO at 774-442-2263. 2. Expanded Fragile X Clinical Research The Child and Adolescent Neurodevelopment Initiative (CANDI, with Co-Directors Drs. Frazier and Kennedy) has two active studies aimed at expanding our knowledge about how to help individuals with Fragile X Syndrome. One of our projects is a neuroimaging study aimed at finding effective ways to help children and teens with developmental challenges undergo MRI without the need for sedation. In our current study, we are enrolling youth between the ages of 7-17

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Inhibitors of STEP as a Novel Treatment of Fragile X Syndrome

Inhibitors 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.

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Simon is Weird and Wonderful

Simon is Weird and Wonderful

“Well, I have Fragile X” Simon is weird and wonderful. He’s friendly and curious and talks non-stop. He’s an athlete and an artist. He’s unbelievably generous and crazy stubborn. He often repeats sentences. When his mom reprimands him for something, he’ll say, “Well I have Fragile X.” His next sentence is often, “I want to get rid of it.” Sometimes he says, “It’s your fault.” What Simon needs most in the world is cable TV, the Internet, and food his mother disapproves of. He loves his room: dark and private and equipped with many screens. He loves babies and pretty girls. He is obsessed with Danica Patrick (but that’s supposed to be a secret). He would like to drive but understands that he needs to learn to read first. “That’s too hard,” he says. What he needs most in the world is love and acceptance: from his family, his friends,

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