Repurposing Available Drugs to Treat Fragile X Syndrome – FRAXA Initiatives

FRAXA Research Foundation was founded in 1994 to fund biomedical research aimed at finding a cure for Fragile X syndrome and, ultimately, autism. We prioritize translational research with the potential to lead to improved treatments for Fragile X in the near term. Our early efforts involved supporting a great deal of basic neuroscience to understand the cause of Fragile X. By 1996, these efforts had already begun to yield results useful for drug repurposing. To date, FRAXA has funded well over $25 million in research, with over $3 million of that for repurposing existing drugs for Fragile X.

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Trial and No Error: Better Outcomes for Clinical Trials in Fragile X Syndrome

Christina Timmerman - Meffert lab

Johns Hopkins researcher Christina Timmerman, PhD, searches for a less subjective method to determine if a drug is working in patients with Fragile X syndrome. Many parents of children with Fragile X syndrome were crushed when promising drug trials were unexpectedly stopped a few years ago because subjective behavior-based outcome measures did not justify continuing the trials. The strong feelings linger today. If all goes well with Christina Timmerman’s research, future drug trials may be able to continue with additional metrics for assessment, until there are advanced treatments or even a cure for Fragile X syndrome.

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NIH Investigator Carolyn Beebe Smith, PhD, Looks to Improve Sleep in Fragile X Syndrome

Our sons with Fragile X Syndrome typically go to bed early and rise early. Sometimes they jump on us while we are sleeping at 3 a.m., excited to start their day. For heaven’s sake, why? The answer may come from Carolyn Beebe Smith, PhD, senior investigator, Section on Neuroadaptation and Protein Metabolism, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. She is studying why children, in particularly boys, with FXS have problems sleeping.

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Kimberly Huber, PhD, Explores Hyperexcitability in Fragile X Syndrome

Dr. Kimberly Huber

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.

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Identifying Biomarkers for Fragile X Syndrome – A Study in Argentina

Bio·mark·er, noun, a distinctive biological or biologically derived indicator of a process, event, or condition. Doesn’t help? Well, it’s perfectly clear to Argentinian researchers Patricia Cogram, PhD, and Paulina Carullo, MD, from the FLENI Institute in Buenos Aires, Argentina. They understand there is an urgent need for validated biomarkers after recent Fragile X syndrome clinical trials have failed on their primary endpoints.

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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.

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Cornell University Researcher Looks to Restore Fragile X Protein in Neurons

Which is the right FMRP for therapeutic development of Fragile X syndrome? When researchers develop effective drugs that reactivate FMRP — the protein that is normally silenced in Fragile X — what in the world will they do next? So ponders Cornell University researcher Samie R. Jaffrey, MD, PhD. Jaffrey, professor, Pharmacology, Weill Cornell Medical College, Cornell University, knows reactivating FMRP will lead to many important questions, such as: Which cell type needs FMRP? How much FMRP protein is needed to restore brain function? Where in the brain will FMRP protein be needed? Where in a neuron will the FMRP needs to be expressed?

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Brain 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.

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Achieving Predictability: Developing Biomarkers for Fragile X Patients

klann lab

New York University scientists make progress developing biomarker signatures and cataloging the types of Fragile X patients who will most likely benefit from new therapies. Take a closer look at your son or daughter with Fragile X syndrome. If you meet another child with Fragile X syndrome, chances are he/she may seem totally different to you, yet everyone is united under a FXS diagnosis. Discovering the biological reasons behind these differences is key to identifying which children will respond to what treatment. But how do you find the ‘prediction formula’? New York University scientists may soon know.

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University of Michigan researcher Peter Todd, MD, PhD, Aims to Selectively Turn the Fragile X Gene Back on in Human Cells

Dr. Haenfler and Dr. Todd

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.

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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.

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Meltdown no more? Targeting Hypersensitivity in Fragile X

Dr. Jonny Lovelace and Dr. Khaleel Razak

We’ve all been there. Our child with Fragile X hears something and becomes excited. Very excited. Hand flapping follows with non-stop jumping and ear-piercing squawking. Nothing helps. No meds. No iPhone. No magic toy. Several minutes go by. Sometimes longer. How many times have you apologized in a grocery store — or restaurant — or at the mall? Wouldn’t it make our lives better if this unpredictable excitability was minimalized or eliminated? That’s the premise behind research being conducted at University of California, Riverside. Principal Investigator Khaleel Razak, PhD, and postdoctoral fellow Jonathan W. Lovelace, PhD, are studying mice genetically altered to mimic the genetic characteristics of humans with Fragile X Syndrome.

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Researcher David Nelson, PhD, Explores New Cell Strategies for Fragile X Syndrome, FXTAS and FXPOI

David Nelson lab

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.

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Double Down: Fragile X Clinical Trial Combines Two Available Drugs

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.

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