Research Updates Archives • Fragile X Research

Integrating Human and Mouse Studies in Fragile X Syndrome – an NIH Center Approach

FRAXA Research Foundation Binder, Devin • Erickson, Craig • Huber, Kimberly • Pedapati, Ernest • Research Updates • Seminar Series December 23, 2020astrocytes, EEG, glutamate, NIH, seizure

FRAXA Seminar Series This virtual seminar series addresses a wide range of current topics in Fragile X research. Hosted by FRAXA and organized by Michael Tranfaglia, MD and Patricia Cogram, PhD, sessions feature outstanding speakers from universities and the biotech and pharmaceutical industries. Presentation Summary Craig Erickson - Translational medicine and mechanistic studies of brain neurophysiology in Fragile X Syndrome: A NIH Center Overview Ernest Pedapati - Network Mechanisms, Biomarkers, and Pharmacology of Fragile X Syndrome in Humans Devin Binder - Network Mechanisms of Neurophysiology and Behavior in mouse models of Fragile X Syndrome Kimberly Huber - FMRP Regulation of local and long-range neocortical circuits in the mouse: Links with EEG phenotypes About the SpeakersCraig A. Erickson, MD Professor of Psychiatry at Cincinnati Children's Hospital and the University of Cincinnati College of Medicine Craig Erickson is the director of the Cincinnati Fragile X Research and Treatment Center. Craig has devoted his career

Dr. Mark Bear 1:1 with FRAXA – Developing Arbaclofen for Fragile X

Eric Welin 1:1 with FRAXA • Bear, Mark • Research Updates December 9, 2020arbaclofen

Seven years ago, arbaclofen (STX209) was pulled from development, disappointing families around the US. Now MIT professor and FRAXA Investigator Dr. Mark Bear has founded Allos Pharma to bring it back. Dr. Bear sat down with FRAXA co-founder Katie Clapp to share the story and next steps.

Arbaclofen Returns After 7 Years!

FRAXA Research Foundation Bear, Mark • FRAXA Updates • Research Updates November 19, 2020December 9, 2020arbaclofen, autism, baclofen, GABA, hyperexcitability

Allos Pharma Inc, a late-stage pharmaceutical company developing therapeutics for neurodevelopmental disorders, has announced the exclusive license rights on IP and documentation for arbaclofen in fragile X syndrome (FXS).

Recruiting: Behavior and Cognition in Fragile X Adults Research Study at Stanford University

FRAXA Research Foundation Recruiting • Research Updates November 6, 2020November 10, 2020MRI

Researchers at Stanford University are conducting a clinical research study to learn about behavior & cognition in adults with intellectual & developmental disabilities. Information learned from this research can ultimately contribute to the development of treatment and intervention.

Positive Results Reported in Phase II Fragile X Clinical Trial of PDE4D Inhibitor from Tetra Therapeutics

FRAXA Research Foundation Berry-Kravis, Elizabeth • Gurney Mark • Has Results • Press Release • Research Updates November 2, 2020December 21, 2020Alzheimer's, autism, BPN14770, FDA, mGluR5, NIH, PDE4, Tetra Therapeutics

Today, Tetra Therapeutics announces the first unequivocally positive phase 2 clinical trial in Fragile X syndrome, press release below. The results do not depend on carving out a subset of patients or post hoc analysis.

Overcoming the Placebo Effect in Fragile X Clinical Trials

Caitlyn Dent, RN, BSN Research Updates October 28, 2020October 28, 2020EEG, fNIRS

In a placebo-controlled clinical trial, some participants are given an experimental medication, while others are given a placebo. Participants do not know whether they are taking medicine or placebo. In theory, this can allow researchers to rule out the placebo effect by comparing outcomes among the two groups. But, per Wexler (2020) “having a strong placebo effect can obscure any real effect of the therapy being investigated”.

Zygel May Improve Behavior in Children With Severe Fragile X, Trial Data Suggest

Fragile X News Today Research Updates October 22, 2020October 22, 2020CBD, FDA

Zynerba presented clinical trial results for Zygel at a recent neurology conference. Zygel, an experimental cannabidiol (CBD) gel, may reduce behavioral abnormalities in children with Fragile X syndrome who have more severe disease.

Healx Drug Repurposing Programme for Fragile X Syndrome

FRAXA Research Foundation Research Updates • Seminar Series October 1, 2020October 1, 2020autism, EEG, Healx, Roche

David Brown, MD, PhD, Ivan Angulo-Herrera, PhD and Anthony Hall of Healx present about the Drug Repurposing Programme for Fragile X syndrome.

Yale Researcher Dr. Elizabeth Jonas 1:1 with FRAXA

FRAXA Research Foundation 1:1 with FRAXA • Jonas, Elizabeth • Research Updates September 18, 2020September 18, 2020

We talk with Dr. Elizabeth Jonas, Professor of Internal Medicine and Neurology at Yale School of Medicine, about her new research suggesting that leaky mitochondria cause some symptoms of Fragile X syndrome. Leaky membranes may also be involved in Parkinson’s Disease and other diseases.

Mechanisms and Biomarkers of Sensory Hypersensitivity in the fmr1 Knockout Mouse

FRAXA Research Foundation Binder, Devin • Razak, Khaleel • Research Updates • Seminar Series August 27, 2020August 27, 2020astrocytes, DOD, EEG, glutamate, Healx, hypersensitivity, matrix metalloproteinase, NIH, seizure, sound

In this Fragile X research webinar we hear from Devin K. Binder, MD, PhD, Professor, University of California at Riverside Medical School and Khaleel Razak, PhD, Professor, University of California at Riverside as they present about Mechanisms and Biomarkers of Sensory Hypersensitivity in the fmr1 Knockout Mouse.

Aripiprazole (Abilify) in the Treatment of People with Fragile X: An Anecdotal Account

Caitlyn Dent, RN, BSN Research Updates July 29, 2020August 5, 2020Abilify, aripiprazole, autism, dopamine, FDA, hypersensitivity, NIH, serotonin, sleep

The aim of this article is to discuss the use of Abilify (generic name: aripiprazole) as a treatment for people with Fragile X syndrome (FXS). As an “off-label” prescription, Abilify targets behaviors such as irritability, aggression, self-injury and severe tantrums.

Brain Organoids and Therapeutic Development for Fragile X and Other Rare Diseases

FRAXA Research Foundation Research Updates • Seminar Series July 15, 2020autism, EEG, ERK, FDA, Healx, sound

This is the first in a series of webinars focused on current topics in Fragile X research. In this webinar we hear from Alysson R. Muotri, PhD, Professor at University of California San Diego Stem Cell Programand Fabio C. Tucci, PhD, Chief Operating Officer and co-founder at Epigen Biosciences, Inc.

Trofinetide Clinical Trial Results Published

FRAXA Research Foundation Research Updates May 29, 2020FRAXA-DVI, Neuren Pharmaceuticals, Rett syndrome, trofinetide

New Zealand-Based Biotech Neuren Pharmaceuticals Has Published Successful Phase 2 Fragile X Clinical Trial. Trofinetide, given to adolescent and adult males with Fragile X syndrome, was shown to be generally safe and was well-tolerated. It also showed preliminary evidence of efficacy. This trial validated a new design which can be used in future trials.

Scientists Find a New Way to Reverse Symptoms of Fragile X

FRAXA Research Foundation Bear, Mark • McCamphill, Patrick • Research Updates • Senter, Rebecca May 20, 2020May 26, 2020Alzheimer's, autism, cancer, glutamate, GSK3, hyperexcitability, hypersensitivity, lithium, mGluR, mGluR5, NIH, seizure

FRAXA Investigator and MIT Professor Mark Bear and his colleagues have identified a valuable new target for Fragile X therapeutics: GSK3 alpha. Several FRAXA research teams previously identified GSK3 beta as a treatment target for Fragile X. The catch is that, so far, GSK3 beta inhibitors have proven too toxic for regular use. Dr. Bear’s new discovery opens up the possibility of developing more selective compounds with less toxicity and fewer side effects. Interestingly, lithium inhibits both GSK3 versions – alpha and beta.

Bear lab (Bear 3rd from left, McCamphill on right)

Ketogenic Diet Eases Symptoms in Fragile X Male Mice

FRAXA Research Foundation Research Updates • University of Wisconsin • Westmark, Cara March 12, 2020March 12, 2020Alzheimer's, amyloid precursor protein, autism, EEG, metformin, NIH, seizure, sleep, sound

The Westmark laboratory continues to study sleep and rest-activity cycles in Fragile X mice as a potential outcome measure that correlates between preclinical and clinical research. The analysis of sleep EEG in the mice has proven more labor intensive than they anticipated, but the team is collaborating with Dr. Rama Maganti’s laboratory at UW-Madison on the development of computer scrips to speed up the analysis.

Fragile X Researcher, Cara Westmark, PhD

Drug Repurposing for Rare Disease and the Future of Health – The Genetics Podcast

FRAXA Research Foundation FRAXA Updates • Healx • Research Updates February 20, 2020February 20, 2020autism, Healx, metformin, minocycline

In this double-bill episode of The Genetics Podcast, Dr. Patrick Short talks to two key rare disease researchers in the field: Dr. Bruce Bloom, CCO of Healx, and Dr. Mike Tranfaglia, CSO of FRAXA. Both draw on their wide-ranging personal and professional experiences to discuss the successes and opportunities of drug repurposing, the power of using machine learning, and the work they’ve been doing to aid in finding effective treatments for Fragile X.

Less Active Immune System Evident in Fragile X Patients, Study Suggests

Fragile X News Today Research Updates February 10, 2020February 10, 2020autism, seizure

People with Fragile X syndrome are more likely to develop infections, but are less susceptible to autoimmune disorders than the overall population, a new study found. Taken together, this suggests that the immune system is underactive in this patient population. The study, titled, “The phenotypical implications of immune dysregulation in Fragile X syndrome,” was published in the European Journal of Neurology.

Results Reported: Using EEG Responses to Sound for Fragile X Drug Discovery

FRAXA Research Foundation Lovelace, Jonny • Razak, Khaleel • Research Updates • University of California at Riverside February 6, 2020February 7, 2020autism, EEG, FDA, Fragile X Meeting, hypersensitivity, mGluR5, minocycline, NIH, sound

Jonathan Lovelace, a FRAXA funded Postdoc at UC Riverside, has made some exciting EEG findings over the past few years studying auditory hypersensitivity in mice and therapeutic drug treatments. A big obstacle in FXS research has been establishing reliable, unbiased, and translation relevant biomarkers that can be used to determine the effectiveness of therapies. One of the most important discoveries they have made is the striking similarity in EEG biomarkers between mice and humans.

Should You Participate in a Fragile X Clinical Trial?

FRAXA Research Foundation Research Updates February 3, 2020February 4, 2020EEG, PDE4, Tetra Therapeutics

A Fragile X clinical trial of a new PDE4D allosteric inhibitor from Tetra Therapeutics is nearly complete. Right now there are 3 remaining spots open to males 18-45 years of age with Fragile X syndrome. Dr. Elizabeth Berry-Kravis at the Rush University Medical Center in Chicago is leading this trial. The drug being studied has a unique mechanism of action that might improve cognitive and memory function.

Drug Tolerance is Likely Culprit Behind the Failure of MGluR5 Clinical Trials

FRAXA Research Foundation Bear, Mark • Massachusetts Institute of Technology (MIT) • McCamphill, Patrick • Research Updates November 19, 2019AFQ056, autism, drug tolerance, GSK3, lithium, mGluR, mGluR5, Novartis, Roche

We have long suspected that the clinical trials of mGluR5 blockers from Novartis and Roche failed because the drug triggered tolerance, losing effect over time. With a $90,000 grant from FRAXA, Dr. Patrick McCamphill, a Postdoctoral Fellow in the MIT lab of Dr. Mark Bear, is investigating. He does indeed find tolerance, and now he is looking for ways to overcome it.

Recruiting: Clinical Study of Non-Invasive EEG for Children Ages 2-7

FRAXA Research Foundation 2017 Grants • 2018 Grants • 2019 Grants • Biomarkers • Boston Children's Hospital • Clinical • Current Research Grants • Nelson, Charles A. • Recruiting • Research Updates • Wilkinson, Carol June 5, 2019February 26, 2020autism, EEG, Pierce Family Fragile X Foundation, sound

Dr. Carol Wilkinson, MD PhD, and Dr. Charles Nelson, PhD, at Boston Children’s Hospital are recruiting children ages 2-7 years with Fragile X syndrome to join a study of brain differences using non-invasive EEG.

Ganaxolone Fragile X Clinical Trial Showed Disappointing Results

Hannah Maria Miles Dijck, Anke Van • Kooy, Frank • Research Updates • University of Antwerp, Belgium February 7, 2019February 12, 2019GABA, ganaxolone, mGluR, NIH

Ganaxolone, an experimental drug from Marinus Pharmaceuticals which targets GABA receptors, did not show promise for Fragile X syndrome in a clinical trial.

FXS Patients’ Social Deficits are Linked to Social Anxiety, Eye-tracking Study Says

Fragile X News Today Cincinnati Children's Hospital • Erickson, Craig • Research Updates February 4, 2019AstraZeneca, autism, AZD7325

Dr. Craig Erickson and colleagues at the University of Cincinnati used eye-tracking technology to understand sociability in Fragile X syndrome. This study affirms what so many parents, caretakers, and educators suspect: people with fragile X want to be social, and it is anxiety – not lack of interest – which usually hold them back. If anxiety could be reduced, more sociability would likely follow. Dr. Erickson is a Fragile X expert and FRAXA investigator who is currently conducting a Fragile X clinical trial of an investigational new drug.

Tetra Announces $40M to Advance BPN14770 for FXS and Alzheimer’s Disease

FRAXA Research Foundation FRAXA Updates • Research Updates December 19, 2018December 19, 2018Alzheimer's, BPN14770, FDA, FRAXA-DVI, PDE4, Tetra Therapeutics

Tetra Discovery Partners has signed a multi-part deal that could bring it up to $160 million, plus royalties, from Shionogi & Co, Ltd, a Japanese major research-driven pharmaceutical company. Tetra currently is conducting an investigational Phase 2 study of BPN14770 in adults with Fragile X Syndrome, an indication for which BPN14770 has received Orphan Drug Designation from the US Food and Drug Administration. This clinical trial was made possible by early work with the FRAXA-DVI and over $200,000 from FRAXA.