Research Updates Archives • Fragile X Research

Mega Green Tea Extract to Treat Fragile X?

Hannah Maria Miles de la Torre, Rafael • Dierssen, Mara • Research Updates August 22, 2018Alzheimer's, estrogen

Green tea is thought to have many benefits, particularly in cognitive function. In 2012-14, FRAXA Research Foundation funded a clinical trial to assess the effects of EGCG (green tea extract) on cognitive function in adults with FXS. Drs. Rafael de la Torre and Mara Dierssen Sotos, principal researchers in Barcelona, Spain, reported many positive results. After the extract was no longer administered, effects remained stable. Memory, attention, and mental flexibility improvements were still observable at least 3 months after treatment ended.

How Promising is CRISPR for Fragile X?

Dave Bjork Research Updates • Todd, Peter August 14, 2018August 15, 2018CRISPR, FXTAS, mGluR, PSD-95

Dave Bjork, Director of Community Relations, recently sat down with Peter Todd, MD, PhD, Assistant Professor in the Department of Neurology in the University of Michigan Medical School. Dr. Todd was recently awarded a FRAXA Research Grant for gene reactivation with the use of CRISPR. In this interview he tells us about CRISPR in Fragile X research, how realistic is it that it could turn the Fragile X gene back on, and if it can really be a cure for Fragile X.

Aripiprazole as a Treatment for Fragile X Syndrome

Hannah Maria Miles Clinical Trials • Erickson, Craig • Research Grant with Results • Research Updates June 28, 2018June 29, 2018Abilify, aripiprazole, autism

Many medications are used to help people with Fragile X cope. But few clinical trials have been done on these drugs. Years ago FRAXA funded Dr. Craig Erickson to run a trial of aripiprazole (aka Abilify). FRAXA guest writer Hannah Miles recently caught up with Dr. Erickson to learn the results of the trial.

Study Examines Behavioral Traits of Fragile X Patients Without Autism

Fragile X News Today Research Updates June 21, 2018June 20, 2018autism

Patients with Fragile X syndrome who don’t meet the cut-off for a diagnosis of autism show a decrease in impulsivity and repetitive questioning over time, when compared with patients who do, a new study shows.

Lysogene Partners with FRAXA Investigator Dr. Hervé Moine to Develop Gene Therapy for Fragile X

FRAXA Research Foundation Moine, Herve • Research Updates April 26, 2018April 26, 2018DgkK

A research project funded by FRAXA has led to new fragile x gene therapy initiative, this time in France. Lysogene, a French biopharmaceutical company working to develop gene therapy treatments for brain disorders, is partnering with FRAXA Investigator Dr. Herve Moine to tackle Fragile X syndrome.

FRAXA Research Grants Drive Big Investments in Fragile X

Dave Bjork Bhattacharyya, Anita • Canal, Clinton E. • Kaczmarek, Leonard • Research Updates • Zhao, Xinyu March 28, 2018July 10, 2018Autifony Therapeutics, FRAXA-DVI, Fulcrum Therapeutics, serotonin, sound

Most people know that FRAXA supports academic research at many institutions such as Harvard University, University of Pennsylvania, Massachusetts Institute of Technology, and Yale University. However, FRAXA is also working with more than 30 pharmaceutical companies around the world. Mike spends a lot of his time advising and collaborating with industry partners.

Now Recruiting: Clinical Study of EEG for Young Boys at Boston Children’s Hospital

FRAXA Research Foundation Clinical Trials • Recruiting • Research Updates March 27, 2018July 10, 2018autism, EEG, Pierce Family Fragile X Foundation, sound

Dr. Carol Wilkinson, MD PhD, and Dr. Charles Nelson, PhD, at the Labs of Cognitive Neuroscience at Boston Children’s Hospital are recruiting young boys with Fragile X syndrome (FXS) to participate in a study investigating how differences in brain activity affect learning, language, and behavior in FXS. If we can determine what distinguishes one brain from another, and if a drug works with a particular neural marker or set of neural markers, this would permit matching drugs based on objective biological markers, a personalized medicine, rather than defaulting to the current method of trial and error.

Can CRISPR Cure Fragile X Syndrome?

Katie Clapp Genetic Rescue • Lee, Jeannie • Research Updates • Todd, Peter February 28, 2018June 4, 2018CRISPR, Rett syndrome

CRISPR/Cas9 was used by MIT researchers to remove the molecular tags that keep the mutant gene shut off in Fragile X syndrome neurons and resulted in some of them producing protein normally. Much work is being done right now, with exciting new discoveries coming at a fast and furious pace.

CRISPR Reactivation of the Fragile X Gene

J. Dora Levin Genetic Rescue • Research Updates • Todd, Peter • University of Michigan December 6, 2017August 6, 2018CRISPR, epigenetics

“We are trying to target the first event that goes wrong in Fragile X syndrome”, says Todd, “One reason our previous attempts to develop treatments for Fragile X syndrome have failed is that they’ve tried to target the downstream effects of losing the Fragile X protein. The protein does many things… bypassing all the functions that it normally takes care of has proven difficult from a pharmacologic perspective.”

Newly Discovered Regulatory Pathways in Fragile X

J. Dora Levin Kaczmarek, Leonard • Research Updates October 31, 2017July 30, 2018Autifony Therapeutics, BK channel, FDA, glutamate, hyperexcitability, hypersensitivity, mGluR5, potassium channels, seizure

Studies at Yale University and elsewhere are showing that FMRP plays a significant role in the regulation of potassium channels. Looking forward, potassium channel opener drugs could rescue some symptoms of Fragile X in humans.

Drug Repurposing Study Results Accelerate Progress Towards Fragile X Treatments

J. Dora Levin Drug Repurposing • Healx • Research Updates October 29, 2017July 11, 2018autism, drug repurposing, FRAXA-DVI, Healx, sleep

While there are over 8,000 rare diseases affecting an estimated 350 million people worldwide, only around 200 of these conditions have effective treatments. Due to the high cost of developing new drugs, rare diseases have historically been less attractive to pharmaceutical companies. Drug repurposing systematically leverages the detailed information available on approved drugs and reduces the time and money needed to deliver safe “new” treatments, but with greater success rates and a potentially more immediate impact on health care.

In Their Own Words: Reports From the International Fragile X Workshop

FRAXA Research Foundation Cogram, Patricia • Contractor, Anis • Events Recap • Kooy, Frank • Lee, Jeannie • McGill University • Moine, Herve • Razak, Khaleel • Research Updates • Smith, Carolyn B. • Sonenberg, Nahum • Todd, Peter • Vanderklish, Peter October 29, 2017June 18, 2018amygdala, autism, bumetanide, DgkK, drug repurposing, EEG, ERK, FDA, Fragile X Meeting, GABA, ganaxolone, glutamate, hyperexcitability, hypersensitivity, metformin, mGluR5, minocycline, mRNAs, Rett syndrome, seizure, sleep, sound

The 18th International Fragile X and Related Neurodevelopmental Disorders Workshop in Quebec, Canada, was a great success, featuring Fragile X much more heavily than any previous meeting in this series! We asked our speakers to summarize their work in their own words. These brief updates from researchers investigating Fragile X.

Brain Imbalance Target of Dr. Erickson’s New Clinical Trial

Theodore Coutilish Biomarkers • Cincinnati Children's Hospital • Clinical • Erickson, Craig • Research Updates October 25, 2017June 15, 2018Abilify, AstraZeneca, autism, AZD7325, EEG, GABA, glutamate

According to Dr. Erickson, AZD7325 is a drug that selectively boosts GABA neurotransmission in the brain. GABA is the primary neurochemical in the brain that blocks brain activation. GABA activity is in balance in the brain with Glutamate activity, which is the primary neurochemical that causes brain activation. In Fragile X, GABA activity is insufficient and glutamate activity is excessive, likely causing brain activity to be out of balance. AZD7325 attempts to correct parts of this imbalance by boosting the insufficient GABA activity in the brains of people with Fragile X

Fragile X in the Forefront of International Conference

FRAXA Research Foundation Events Recap • Research Updates October 12, 2017June 18, 2018autism, Fragile X Research Foundation of Canada, Fulcrum Therapeutics, Ovid Therapeutics

Today the 18th International Fragile X and Related Neurodevelopmental Disorders Workshop kicks off in Quebec, Canada. For the next six days, scientists from around the world will gather at this workshop to focus on recent breakthroughs in our understanding of Fragile X, autism spectrum disorders (ASD), and related neurodevelopmental disorders. This biennial meeting has been instrumental to the discovery of many disease-causing genes and the development of therapeutic strategies for these disorders.

Neural Markers of Fragile X: A Powerful New Tool for Clinical Trials

J. Dora Levin Biomarkers • Boston Children's Hospital • Clinical • Harvard University • Nelson, Charles A. • Research Updates • Wilkinson, Carol August 17, 2017July 30, 2018Autifony Therapeutics, autism, EEG, hypersensitivity, ion channel, Pierce Family Fragile X Foundation, sleep, sound

Once the neural marker is identified for a particular challenge, such as kids with poor language versus good language, neural markers can be measured during drug and behavioral therapy trials to see if a child is improving based on objective biological measures.

Targeting Serotonin Receptors to Treat Behavioral and Psychological Symptoms

Theodore Coutilish Canal, Clinton E. • Disease Mechanisms • Drug Repurposing • Mercer University • Research Updates August 1, 2017June 15, 2018drug repurposing, serotonin

With a $90,000 grant from FRAXA Research Foundation awarded in 2017, Dr. Clinton Canal targets seratonin receptors. “There are 15 unique serotonin receptors (at least) and many of them impact the function of brain circuits that are impaired in neurodevelopmental and psychiatric disorders,” said Dr. Canal. “Results from this project could guide new drug discovery or drug repurposing for Fragile X.”

FRAXA Wins Award for Drug Repurposing

FRAXA Research Foundation FRAXA Updates • Research Updates June 26, 2017May 3, 2018drug repurposing, lithium, metformin, minocycline

Cures Within Reach, the leading global nonprofit focused on repurposing research as a fast track to saving patient lives, has awarded FRAXA Research Foundation the 2017 Golan Christie Taglia Patient Impact Philanthropy Award for efforts to find treatments for the rare disease Fragile X syndrome.

Metformin, Diabetes Drug, Potential Fragile X Treatment

Theodore Coutilish Drug Repurposing • McGill University • Research Updates • Sonenberg, Nahum May 18, 2017August 6, 2018autism, cancer, metformin, MMP9, Roche, sleep

“We treated mice with metformin and corrected all the core Fragile X deficits. We are optimistic about using metformin in human clinical trials. This is a generic drug with few side effects” says Nahum Sonenberg, PhD, James McGill Professor, Department of Biochemistry, McGill Cancer Center, McGill University.

Fragile X Nervous (System) Breakdown

Theodore Coutilish Disease Mechanisms • Research Updates March 21, 2017June 14, 2018

“The occurrence and development of events by chance in a happy or beneficial way.” That’s how Lynne E. Maquat, PhD, describes the process of how her research extended to Fragile X syndrome to better understand it and ultimately find advanced treatments.

Did Tolerance Result in Fragile X mGluR5 Clinical Trial Failures?

Theodore Coutilish Bear, Mark • Massachusetts Institute of Technology (MIT) • Research Updates • Senter, Rebecca March 15, 2017June 14, 2018AFQ056, drug tolerance, glutamate, mGluR, mGluR5, Novartis, Roche

Although the clinical trials failed to show efficacy in the patient population and Novartis and Roche discontinued their Fragile X development programs, Dr. Senter has worked with Mark Bear, PhD to carefully review parent observations. Those caregiver reports suggested tolerance to mGlu5 antagonists antagonists developed quickly, consistent with some preclinical findings in the mouse model.

Repurposing Available Drugs to Treat Fragile X Syndrome – FRAXA Initiatives

Michael Tranfaglia, MD Drug Repurposing • Research Updates February 10, 2017July 26, 2018arbaclofen, autism, baclofen, drug repurposing, FRAXA-DVI, glutamate, GSK3, Healx, hypersensitivity, lithium, lovastatin, MAP1b, matrix metalloproteinase, metformin, mGluR, minocycline

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. Here are some examples of FRAXA-funded work on repurposing available drugs for Fragile X syndrome: Lithium In the mid-1990s, the Greenough lab at the University of Illinois discovered that FMRP, the protein missing in Fragile X, is rapidly translated in dendrites in response to stimulation of glutamate receptors. FRAXA funded preclinical validation of this discovery in theRead more

Fragile X Research Tackles High Anxiety – Peter Vanderklish

Theodore Coutilish Disease Mechanisms • Research Updates • Scripps Research Institute • Treatment Targets • Vanderklish, Peter February 9, 2017July 26, 2018hypersensitivity

Yes, we all know the signs of Fragile X anxiety: Ears begin turning red followed by incessant pacing, heavy breathing, stiffening body, flapping, jumping, avoidance or yelling. Sometimes, it’s the more severe screaming, pinching, scratching, biting and general tearing things up or, worse, the nuclear meltdown.

FRAXA Plans for Fragile X Research: 2018 Funding Opportunities

Michael Tranfaglia, MD FRAXA Updates • Research Updates February 5, 2017February 14, 2018

FRAXA Research Foundation will fund over $1 million in research aimed at finding new and improved treatments — and ultimately a cure — for Fragile X syndrome. Research applications are due February 1, 2018. Clinical trial proposals are accepted anytime. Every year we receive proposals from scientists worldwide seeking funding for the most cutting-edge Fragile X research.

University of Cambridge Startup Healx is Rapidly Identifying Existing Drugs to Help Fragile X Patients

Theodore Coutilish Drug Repurposing • Healx • Research Updates January 9, 2017July 2, 2018drug repurposing, Healx

FRAXA awarded $44,000 to Healx in 2017 for drug repurposing to find new treatments for Fragile X syndrome. The results of this study include eight top “hits” which show promise for Fragile X. FRAXA is further investigating these hits.

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

Theodore Coutilish Clinical • Research Updates December 14, 2016July 2, 2018

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. This will be welcome news to parents. Timothy Gamache, graduate student, and Christina Timmerman, PhD “We hope a more quantitative outcome measure, such as the proposed microRNA biomarker, would allow for a less subjective method to determine if a drug is working or not,” said Dr. Timmerman, Postdoctoral Fellow, Lab of Mollie Meffert, DepartmentRead more

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