sleep Archives • Fragile X Research - FRAXA Research Foundation

Screening 2,320 FDA-Approved Drugs for Potential Treatment of Fragile X

FRAXA Research Foundation 2018 Grants • 2019 Grants • Current Research Grants • Disease Mechanisms • Joyce, Karen • McBride, Sean • Rowan University • Treatment Targets January 9, 2019January 31, 2019FDA, fruit fly, lithium, metformin, mGluR, sleep

FRAXA Research Foundation has awarded a $90,000 grant to Principal Investigator Dr. Sean McBride and Postdoctoral Fellow Dr. Karen Joyce, at Rowan University, to screen all 2,320 FDA-approved drugs on both mouse and fly models of Fragile X syndrome. Those drugs which show promise will be tested in more detail for potential to treat Fragile X in humans.

Coffee, Tea, and Chocolate: Adenosine Receptors in Fragile X

FRAXA Research Foundation 2018 Grants • Borreca, Antonella • Current Research Grants • Disease Mechanisms • Italian National Institute of Health • Martire, Alberto • Treatment Targets December 11, 2018February 7, 2019AMPAkines, BDNF, cyclic AMP, glutamate, mGluR5, mRNAs, sleep

Caffeine is the most popular smart drug in the world. With a $90,000 grant from FRAXA Research Foundation, Alberto Martire, PhD and Antonella Borreca, PhD in Rome, Italy are investigating adenosine receptors antagonists to treat Fragile X syndrome. Compounds which are able to block adenosine receptors are commonly found in tea, chocolate, and coffee.

Tetra Discovery Partners Initiates Phase 2 Trial of BPN14770 in Fragile X Syndrome

FRAXA Research Foundation Berry-Kravis, Elizabeth • Rush University Medical Center July 10, 2018January 14, 2019Alzheimer's, autism, BPN14770, FDA, PDE4, sleep, Tetra Therapeutics

This 2-Period Crossover Study of BPN14770 is accepting adults males with Fragile X syndrome at Rush University Medical Center in Chicago. Principal Investigator of the study is Elizabeth Berry-Kravis, MD, PhD.
A selective inhibitor of the phosphodiesterase type-4D (PDE4D), BPN14770 has shown the ability to improve the quality of connections between neurons and to improve multiple behavioral outcomes in the Fragile X mouse model.

Drug Repurposing Study Results Accelerate Progress Towards Fragile X Treatments

J. Dora Levin Drug Repurposing • Healx • Research Updates October 29, 2017July 11, 2018autism, 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, 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.

Clinical Trial of Ganaxolone in Patients with Fragile X Syndrome

FRAXA Research Foundation 2014 Grants • 2015 Grants • Clinical • Dijck, Anke Van • Kooy, Frank • Research Grant with Results • Treatment Targets • University of Antwerp, Belgium September 2, 2017March 27, 2019GABA, GABA-A, ganaxolone, glutamate, seizure, sleep

With a $90,000 grant from FRAXA Research Foundation funded during 2014-2015, Dr. Frank Kooy and colleagues at the University of Antwerp are conducting a double blind crossover trial of ganaxolone in patients with Fragile X syndrome. Results of this study were mixed (see Marinus: Results from Phase 2 Exploratory Clinical Study Support Continued Development of Ganaxolone in Fragile X Syndrome.

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, 2017June 20, 2019Autifony 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.

Preclinical Testing of Sleep-Wake Patterns as an Outcome Measure for Fragile X

Theodore Coutilish 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Current Research Grants • Treatment Targets • University of Wisconsin • Westmark, Cara May 23, 2017August 29, 2018Alzheimer's, amyloid precursor protein, autism, EEG, seizure, sleep, sound

FRAXA Research Foundation awarded $122,000 over 2016-2018 to Dr. Cara Westmark at the University of Wisconsin at Madison for studies of sleep disorders in Fragile X syndrome.

Metformin, Diabetes Drug, Potential Fragile X Treatment

Theodore Coutilish Drug Repurposing • McGill University • Research Updates • Sonenberg, Nahum May 18, 2017January 9, 2019autism, cancer, matrix metalloproteinase, 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.

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

Theodore Coutilish Research Updates • Smith, Carolyn B. November 17, 2016July 2, 2018Alzheimer's, autism, baclofen, FDA, lithium, sleep

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, wHY, 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. “We know sleep is important for many aspects of brain function,” said Dr. Smith, who received a PhD from the University of London where she studied the chemical pathology of Alzheimer’s for which she was awarded the Queen Square Prize. “In studies of healthy mice, we have shown restricted sleep during brain development can result in long-lasting changes in behavior. We are interested in understanding if sleep problems contribute to severity ofRead more

Altered Sleep in Fragile X Syndrome: Basis for a Potential Therapeutic Target

FRAXA Research Foundation 2016 Grants • 2017 Grants • 2018 Grants • Biomarkers • Current Research Grants • Disease Mechanisms • National Institute of Mental Health • Smith, Carolyn B. • Treatment Targets September 5, 2016January 3, 2019sleep

With a $90,000 grant from FRAXA Research Foundation over 2016-2018, Dr. Carolyn B. Smith and Dr. Rache Sare at the National Institute of Mental Health investigated the basis of sleep problems in Fragile X syndrome.

Fragile X Fruit Fly Research Bears Fruit

FRAXA Research Foundation Jongens, Tom • McBride, Sean • Research Updates April 26, 2016August 1, 2018autism, fruit fly, metformin, sleep

Sean McBride, MD, PhD, and Thomas Jongens, PhD, of the University of Pennsylvania 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 treat the behavioralRead more

Fragile X Cure One Step Closer with FRAXA Support of $1 Million in New Research

Katie Clapp Research Updates April 26, 2016July 26, 2018CRISPR, hypersensitivity, NMDA, sleep

4 Countries – 10 Teams – $1 Million From finding new treatment targets, to pinpointing outcome measures for future clinical trials, to attempting to reactivate the gene which is silenced in Fragile X syndrome, these innovative scientists will bring us closer to a cure. Improving Clinical Trials Many parents of children with Fragile X know well the struggles of getting their children to sleep through the night. Mice and fruit flies engineered to mimic Fragile X Syndrome also have disrupted sleep. Drs. Westmark and Smith will test potential therapeutics in mice using sleep as an outcome measure and investigate whether sleep could be used as an outcome measure for future clinical trials. The search is on for a simple blood test to measure how well a treatment works for an individual with Fragile X. Dr. Frank Kooy's team investigates. Testing Treatment Targets One of the goals of FRAXA’s research program has been to find biological pathwaysRead more

GABA-A Receptor in Fragile X Syndrome

Katie Clapp 1994-2000 Grants • 2006-2010 Grants • Completed Research Grant • Disease Mechanisms • Kooy, Frank • University of Antwerp, Belgium October 19, 2014January 23, 2019GABA, GABA-A, sleep

With $210,000 in grants from FRAXA over 1999-2010, Dr. Frank Kooy has studied the involvement of the GABAergic system in Fragile X syndrome, at the University of Antwerp, Belgium.

Sleep and Circadian Rhythms in Fragile X Mutant Drosophila

FRAXA Research Foundation 2006-2010 Grants • Allada, Ravi • Completed Research Grant • Disease Mechanisms • Northwestern University February 14, 2008April 28, 2018fruit fly, sleep

With an $80,000 grant from FRAXA Research Foundation over 2 years, Dr. Ravi Allada and his team studied at Northwestern University sleep behaviors in Fragile X fruit flies. These fruit flies are useful for several important reasons; not only do they have a good cognitive phenotype, they also have a clear disturbance of circadian rhythms. This is an important model for human hyperactivity and sleep disorders, and this group studied the underlying mechanisms in an effort to find treatments for the human conditions.

Melatonin Clinical Trial in Fragile X

FRAXA Research Foundation 1994-2000 Grants • Clinical • Clinical Trials • Completed Research Grant • Disease Mechanisms • Hagerman, Randi • Treatment Targets • University of California at Davis February 27, 2000August 13, 2018autism, melatonin, serotonin, sleep, sound

With a $60,000 grant from FRAXA Research Foundation from 1998-1999, Dr. Randi Hagerman and her team at the University of California studied the effects of different compounds on individuals with Fragile X syndrome, focusing specifically on melatonin. Results published.