Boston Bruins Grant Funds New Fragile X Research

Boston Bruins Grant Funds New Fragile X Research

Boston Bruins Foundation’s $90,000 commitment to FRAXA Bruins Foundation Executive Director Bob Sweeney pledging a $90,000 donation to FRAXA Research today at Shared Living Collaborative’s Gateway Farm in Merrimac, MA. The award will enable the organization to fund an entirely new research project aimed at developing new treatments for Fragile X, a genetic syndrome that is the most common inherited cause of autism. #NHLBruins A photo posted by Boston Bruins (@nhlbruins) on May 28, 2015 at 10:29am PDT The new fellowship to be funded by this award goes to Drs. Lynne Maquat and Tatsuaki Kurosaki of the University of Rochester. They 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 — and so If this project

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New 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. “Our results suggest that to have the greatest therapeutic benefit, we may need to make sure we’re blocking all of this type of receptor, both inside and on the surface of the cell.”  “This should be a factor we consider when we design drugs to target brain cell receptors. Do we want to reach cell surface receptors, receptors inside the cell

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Scientists Uncover Trigger for Fragile X syndrome

Finding May Explain Many Brain Disorders, Lead to Prevention and Treatment adapted from Weill Cornell Medical College press release   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. While researchers have known for more than two decades that the culprit behind Fragile X is an unusual mutation characterized by the excess repetition of a particular segment of the genetic code, they weren’t sure why the presence of a large number of these repetitions – 200 or more – sets the disease process in motion. Using stem cells from donated human embryos

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Lovastatin discovery in Fragile X mice leads FRAXA to fund Clinical Trials

Lovastatin discovery in Fragile X mice leads FRAXA to fund Clinical Trials

Available medication Lovastatin corrects excess protein synthesis in Fragile X mice At the opening dinner of the 2011 FRAXA Investigators Meeting in Southbridge, MA,  Dr. Emily Osterweil was awarded the FRAXA Pioneer Award  for work demonstrating that Lovastatin could treat Fragile X.  Dr. Osterweil conducted her experiments in the MIT laboratory of Dr. Mark Bear; she has since established her own laboratory at the University of Edinburgh. The team discovered that lovastatin, a drug widely prescribed for high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent epileptogenesis. The work is published in the prestigious neuroscience journal Neuron: Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome. One implication of the mGluR theory of Fragile X is that there are exaggerated consequences of activation of signaling pathways which link metabotropic glutamate receptors (mGluRs) to the cellular machinery of neurons. It

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2013 FRAXA Investigators Meeting: Treatment Strategies for Fragile X

September 29-October 2, 2013 Southbridge Hotel and Conference Center Southbridge, MA We are pleased to announce that registration is open for the 2013 FRAXA Investigators Meeting. We expect another lively meeting with presentations of recent advances in the field of Fragile X research. This meeting, as with past ones, will provide ample opportunity for discussion, debate and collaboration. Meeting Announcement Preliminary Meeting Outline Registration Form Presentation Preference Form

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Phase 2b Clinical Trial of Arbaclofen in Autism Has Disappointing Results

Phase 2b Clinical Trial of Arbaclofen in Autism Seaside Therapeutics reports the study did not show improvement on the primary endpoint of social withdrawal, but it did demonstrate improvement on the Clinical Global Impression of Severity scale. Read the article: http://www.marketwatch.com/story/seaside-therapeutics-to-announce-results-from-a-phase-2b-clinical-trial-of-arbaclofen-in-autism-spectrum-disorder-at-the-international-meeting-for-autism-research-imfar-2013-conference-2013-05-01

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FRAXA Finances – the numbers 2010-2013

FRAXA Finances – the numbers 2010-2013

FRAXA has funded more than $22 million in research at universities all over the world. But fundraising has been challenging over the past few years. But the driving force behind FRAXA is parents who are determined to help their children. We’ve kept overhead expenses very low in order to devote as many dollars as possible to Fragile X research! 2012  Income Donations & Grants 1,390,944 (79%) Fundraising 243,881 (14%) Investments 120,183 (07%) Product & Royalties 5,287 (00%) Total:   1,760,294 (100%) Expenses Fundraising 82,254 (04%) Management/General 58,521 (03%) Program – Education 129,150 (07%) Program – Research 1,645,339 (86%) Total Expenses 1,915,265 (100%) Net Income -154,971 2011 Income Donations/Grants 1,109,353 (75%) Fundraising 351,617 (24%) Investments 9,913 (01%) Product & Royalties 5,603 (00%) 1,476,486 (100%) Expenses Fundraising 70,504 (04%) Management/General 57,378 (03%) Program – Education 99,408 (06%) Program – Research 1,583,573 (87%) Total Expenses 1,810,864 (100%) Net Income -334,377 2010 Income Donations/Grants 1,447,344 (73%) Fundraising

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Clinical Trials FAQ ← frequently asked questions

Question: How do families decide which trial is best for them? Answer: Each of the trials has different requirements for joining, so many – if not most – people will only be eligible for one trial after screening. The best way to approach this is to call the clinic contact closest to your area and discuss this with him/her. Age, weight, current medications, behavior, and IQ are all factors. When will the trials be finished? It all depends on enrollment. Right now, the Novartis trial and the Seaside trial are well underway and the Roche trial is just getting started. The trials need to have a certain number of people (a number determined before the trial starts) complete the trial before they can analyze the data and present results to the FDA. Right now, there is hope that the Novartis and Seaside trials could complete their enrollment by the end

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Darren’s Smile

Darren’s Smile – This is a very difficult post to write because it is about a son, Darren, who has passed away. Darren’s dad has written a memoir – a beautiful tribute to his son. Darren had Fragile X syndrome. He lived a rich life and was very much loved. Sadly he died because of a choking incident at the group home where he lived. There’s not much written about the risk of choking for people who have Fragile X, but I do wonder if it is a particular risk that we should remember. Read Darren’s Smile at http://fraxa.org/pdf/Darren.pdf

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FRAXA Progress and Future Plans

It’s official: Fragile X is now the hottest research topic in all of neuroscience! Just last month, massive publicity attended the publication of Fragile X clinical trial results and major papers by FRAXA’s outstanding translational researchers. Even as news of the first round of Fragile X clinical trials is emerging, Phase III trials (which can lead to actual marketing of medications) are under way and slated to finish around the end of the year. This is exciting, and it is just the tip of the iceberg. Thanks to your support, FRAXA has developed an entire pipeline of disease-modifying treatments for Fragile X. We started years ago by funding basic research to understand the cause of Fragile X; we then recruited dozens of the world’s finest neuroscientists to look for ways to fix the underlying problems. Many promising treatment strategies have emerged. Some are existing medications that no one imagined would

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What works, and what doesn’t

At the start, it’s always hard to know what methods will work best for something as complex as the development of disease-modifying treatments for fragile X. But, we’ve always tried to let the science lead us down the right path. At this point, the results are unequivocal, and they have shaped how we are looking for the Next Great Thing in fragile X treatments. As a bit of background, it’s worth noting that there are two basic ways of approaching treatment research for any disease: rational drug discovery vs. high-throughput screening. Rational drug discovery means exploring the basic mechanism of disease and identifying specific “treatment targets” that might be expected to correct the underlying problem. Usually, the target is an enzyme (a protein which facilitates biochemical reactions in the cell) or a receptor (a protein, usually on the cell surface, which detects small amounts of a chemical messenger, such as

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Spreading Sunshine

There was a time when no one ever heard about Fragile X. The days seemed darker and colder back then. When a woman named Doris Buffett decided to embrace us, her warmth spread over us like a blanket, and the impact of her presence was immediate. As mothers and fathers of Fragile X children, we felt encouraged by the light Doris cast our way. We felt honored that the Sunshine Lady and her Foundation directors chose to invest in our children and our future. We were reinvigorated because of her generous financial support and her profound vision. Her tremendous energy turned contagious, fueling us to do more. Doris called FRAXA “The Gold Standard” in grass roots charities and donated more than $3 million to FRAXA in challenge grants. With our deepest gratitude, we are once again thanking Doris Buffett’s Sunshine Lady Foundation for her latest gift, a donation which will

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FRAXA Research Outlook 2012 – Treatment Trials and the Next Wave of New Drugs

Treatment Trials As you probably know, three pharmaceutical companies are conducting clinical trials in Fragile X. Two Swiss giants, Novartis and Roche, are racing to get their lead mGluR5 antagonists to market, and U.S. startup Seaside Therapeutics is pursuing a compound which targets the brain receptor, GABAB. Novartis has large-scale Phase IIb/III trials of the drug AFQ056 well underway. Sites worldwide are enrolling adolescents and adults, with 35 more adults needed and recruitment of adolescents planned through Fall 2012. At this point, some participants have already completed the placebo-controlled trial and are now taking AFQ056, with the option of continuing it until it reaches the market. Novartis is also working toward a trial of AFQ056 for younger children with Fragile X. Roche completed a Phase II trial of its mGluR5 antagonist (currently with the catchy name of RO4917523) last year and is about to commence a larger Phase II trial

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FRAXA 2010 Research Awards Funded

4/1/2010 Program Grants and new Postdoctoral Fellowships total over $1.5 million this year. We are very pleased to announce FRAXA 2010 awards. Projects can be viewed at the Research Reports section of this website. These scientists have demonstrated outstanding potential of their FRAXA projects in detailed applications. We aim to help them work toward new treatments for Fragile X. Their projects are at the cutting edge of biomedical technology, and we believe that their work will make a real difference to everyone affected by Fragile X. FRAXA is collaborating with more than a dozen pharmaceutical companies to translate this research into practical treatments for Fragile X. In May, 100 FRAXA-supported researchers will join many of these pharmaceutical industry scientists at the FRAXA Investigators Meeting. There they will put their heads together for our common goal: finding effective treatments and a cure for Fragile X. We extend our most sincere gratitude

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Roche begins New Phase 2 Fragile X Clinical Trial in the US

Swiss pharmaceutical giant Hoffmann-LaRoche (“Roche”) has begun US trials of their lead mGluR5 antagonist, RO4917523, for Fragile X. Five US sites – Atlanta, Chicago, Nashville, Indianapolis, and Davis, CA – are currently recruiting participants; details here. Longtime FRAXA members will recall that we’ve been talking about the promise of mGluR5 drugs to treat Fragile X for years. Ever since FRAXA Postdoctoral Fellow Dr. Kim Huber made the original finding in Mark Bear’s lab at Brown University in 2000, FRAXA has been working nonstop to organize and fund the pivotal preclinical research which has validated these drugs as potential treatments for Fragile X. Starting in 2001, FRAXA organized a concerted effort in university labs around the world to confirm Mark Bear’s mGluR Theory of Fragile X and to demonstrate to pharmaceutical companies that mGluR5 antagonists have specific therapeutic effects for Fragile X. This strategy has exceeded expectations with trials currently in

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Composition and Localization of Dendritic mRNAs in Fragile X Syndrome

Composition and Localization of Dendritic mRNAs in Fragile X Syndrome
Drs. Smith and Wang are investigating which proteins, as well as the mRNA's that code those proteins, are dysregulated in Fragile X. They have developed a elegant system to visualize the proteins and mRNA's and determine where they are spacially in the neuron. This will help to better understand the root causes of Fragile X syndrome and to design targeted treatments. $80,000 Grant Stephen Smith, PhD Principal Investigator Stanford University 2008-2009 FRAXA Research Grant $80,000 over 2 Years A Quantitative Study by Array Tomographic Florescent In Situ Hybridization by Gordon Wang, 8/1/2008 Fragile X syndrome is caused by the malfunction of a fundamental cellular process, the ability of cells to regulate spatially distinct pools of messenger RNA (mRNA). One of the cell types most affected is the neuron. This highly asymmetric cell type relies upon a tightly orchestrated network of proteins and RNAs to acutely and focally deal with its basic function,Read more

Results of first fenobam trial in adults with Fragile X Published

Results of first trial of fenobam in adults with Fragile X Published in Major Journal We are pleased to announce the publication of positive results of a Phase IIa clinical trial of fenobam in Fragile X. Fenobam belongs to a class of compounds known as mGluR5 antagonists. Neuropharm, a specialty pharmaceutical company based in the U.K., received Orphan Drug Designation in the US in 2006 for fenobam in the treatment of Fragile X, after acquiring rights to relevant data on the compound from FRAXA. This trial was conducted in the US by Drs. Randi Hagerman of the UC Davis MIND Institute and Elizabeth Berry-Kravis of the RUSH University Medical Center, and initial results were first announced last summer. Their article in the Journal of Medical Genetics can be accessed free at: http://jmg.bmj.com/cgi/rapidpdf/jmg.2008.063701v1 Highlights of the study: 1. This was a single dose open label study of fenobam in 6 male

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3 Researchers Honored at FRAXA Investigators Meeting

Three researchers honored at FRAXA 2008 Investigators Meeting Over 150 scientists from around the globe gathered in Durham, New Hampshire, for FRAXA Research Foundation’s Investigators Meeting on September 21-24, 2008. They came from Australia, Canada, India, Turkey, the U.S., and eight European countries. Their common goal: “to share, collaborate and publish,” in the words of FRAXA’s Medical Director, Michael Tranfaglia, MD, to find effective treatments and a cure for Fragile X, the foremost inherited cause of mental retardation and autism. Most of the attendees were university-based professors, postdoctoral fellows, and graduate students who have FRAXA research grants. Also participating in the meeting were scientists from the National Institutes of Health (NIMH, NICHD, and NINDS), Neuropharm Group PLC, Hoffman LaRoche Inc., GlaxoSmithKline, Indevus, and Seaside Therapeutics, as well as 20 parents of Fragile X children. At the opening reception, FRAXA honored three investigators for taking extraordinary steps to advance research: *

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Researchers Propose Minocycline to Treat Fragile X

Study leader Iryna Ethell awarded FRAXA Breakthrough Award for 2008 A University of California Riverside team of scientists has found that an available drug called minocycline, used widely to treat acne and skin infections, might also be used to treat Fragile X. The study’s findings have already led to the approval of a FRAXA-funded clinical trial in Toronto, Canada, that will test minocycline in patients with Fragile X. Neurons in the brain communicate with each other at specialized contact sites called synapses, with many of these synapses occurring on small mushroom-shaped structures called dendritic spines. During early development dendritic spines have immature finger-like shapes. But learning stabilizes the synapses and dendritic spines take on a mature mushroom shape, which make them more efficient. The brains of patients with Fragile X syndrome have an overabundance of immature dendritic spines. In their report, the researchers, led by Iryna Ethell and Douglas Ethell,

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Phase II Trial of Fragile X Treatment in Europe: AFQ056

This small Phase II trial sponsored by Novartis will test a new compound which is an mGluR5 antagonist. A new trial has been posted today at ClinicalTrials.gov: Efficacy, Safety and Tolerability of AFQ056 in Fragile X Patients. AFQ056 is a new compound developed by Novartis; it’s their lead mGluR5 antagonist, which means it reduces mGluR5 activity in the brain. This, as many FRAXA-supported research studies have shown over the past few years – is known to be overactive in Fragile X. This trial, conducted in Italy, France, and Switzerland, will evaluate the safety, tolerability and efficacy of multiple doses of AFQ056 in patients with Fragile X Syndrome. The dose range will be 50 to 150 mg twice daily. The primary read-out of efficacy is reduction in Aberrant-Behavior Checklist score, a standard and widely-accepted measure of mental health. Enrollment is by invitation only. AFQ056 is also being studied as a potential

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FRAXA Grant to Carlos Paribello, PhD — Fragile X Research Foundation of Canada

FRAXA Awards: $40,000 in 2008 This trial is based on results of another FRAXA-funded study of minocyline in mice, by the Ethell lab at UC-Riverside. Add-On Pilot Trial of Minocycline in Fragile X Report: 12/1/2008 Researchers funded by FRAXA have discovered that a drug called minocycline can reverse structural abnormalities seen in the brain cells of Fragile X mice. Minocycline belongs to a group of antibiotics called synthetic tetracyclines, and it has been used in people for more than fifty years to treat Lyme disease, acne, and other skin infections. With a $40,000 grant from FRAXA, Dr. Carlo Paribello and his team at the Surrey Place Centre Fragile X clinic in Toronto, Ontario, are running an open label trial to see if minocycline can improve learning and reduce anxiety and behavioral problems in people with Fragile X. Twenty participants between the ages of 13 and 35 years take minocycline for

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