Non-Invasive Imaging as a Biomarker for Future Fragile X Clinical Trials

Non-Invasive Imaging as a Biomarker for Future Fragile X Clinical Trials

FRAXA Research Foundation has renewed Kamilla Castro’s 2017 FRAXA Fellowship for a second year. With this $90,000 award, Kamilla Castro and Principal Investigator Dr. Andreas Frick are using non-invasive magnetic resonance imaging (MRI) methodology to assess connectivity changes in the brain in Fragile X. If this project is successful, we will have objective outcome measures to evaluate new treatments, both in mice bred to mimic Fragile X and in human patients.

Read more

Auditory Dysfunction in Fragile X Syndrome, Role for the Sound Localization Pathway

Auditory Dysfunction in Fragile X Syndrome, Role for the Sound Localization Pathway

FRAXA Research Foundation has renewed Dr. Elizabeth McCullagh’s 2017 FRAXA Fellowship for a second year. Dr. McCullagh and Principal Investigator Dr. Achem Klug are investigating the “cocktail party effect” in Fragile X mice. There is a specific circuit which allows us to discriminate between competing sound sources, helping us focus on a sound source of interest such as with a conversation partner. If clear differences are found in this circuit, they could be used as potential biomarkers for Fragile X clinical trials.

Read more

Neural Markers of Cognitive, Language and Behavioral Deficits in Children with Fragile X

Neural Markers of Cognitive, Language and Behavioral Deficits in Children with Fragile X

This 2017 grant of $90,000 over two years enabled Dr. Wilkinson to study EEG in young children with Fragile X syndrome at Boston’s Children’s Hospital. She is working with principal investigator, Dr. Charles Nelson, Professor of Pediatrics at Harvard Medical School and a specialist in cognitive neuroscience. Co-funded by the Autism Science Foundation and the Pierce Family Fragile X Foundation.

Read more

Fragile X Clinical Trial of AZD7325 in Adults

Fragile X Clinical Trial of AZD7325 in Adults

With a $51,000 grant from FRAXA Research Foundation, Dr. Craig Erickson will conduct a double-blind, placebo-controlled clinical trial of AZD7325 in adults with Fragile X syndrome at Cincinnati Children’s Hospital.  The compound being studied is an investigational new drug from AstraZeneca that targets GABA (A) receptors.

Read more

Connectivity as a Biomarker for Future Fragile X Clinical Trials

Connectivity as a Biomarker for Future Fragile X Clinical Trials

With a 2017 grant from FRAXA Research Foundation of $90,000, Dr. Andreas Frick’s team at Neurocentre Magendie, in France, will test non-invasive imaging using magnetic resonance imaging (MRI) as a potential biomarker for future Fragile X syndrome clinical trials.

Read more

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

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

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

Read more

Clinical Trial of Combined Treatment of Minocycline and Lovastatin in Fragile X Syndrome

Clinical Trial of Combined Treatment of Minocycline and Lovastatin in Fragile X Syndrome

With a $66,714 grant from the FRAXA Research Foundation awarded over 2015-2017, Dr. Francois Corbin at the Universite of Sherbrooke will test the safety and synergistic effects of lovastatin and minocycline in patients with Fragile X syndrome.

Read more

Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers

Combinatorial Drug Treatment in a Model of Fragile X Syndrome using Novel Biomarkers

With a $90,000 grant from FRAXA Research Foundation awarded over 2016-2017, University of California researchers Khaleel Razak, PhD, and Jonathan W. Lovelace, PhD, are exploring drug combinations to limit hypersensitivity to sounds in Fragile X mice.  

Read more

Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI)

Fragile X Syndrome Drug Validation Initiative (FRAXA-DVI)

The FRAXA Drug Validation Initiative (FRAXA-DVI) provides speedy, cost-effective, objective preclinical testing of potential new Fragile X treatments. FRAXA has funded FRAXA-DVI for $50,000 or more per year since 2012.

Read more

Defining the Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists

Defining the Subcellular Specificity of Metabotropic Glutamate Receptor (mGluR5) Antagonists

With $217,500 in grants from FRAXA Research Foundation, Dr. Karen O’Malley and team studied the function of mGluR5 when it is inside cells. Many of the symptoms of Fragile X Syndrome (FXS) are thought to arise due to overactive metabotropic glutamate receptor 5 (mGluR5) signaling, which is normally opposed by the protein missing in FXS, Fragile X Protein (FMRP).

Read more

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

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

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.

Read more

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

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

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.

Read more

Biomarker Discovery and Validation for Fragile X Syndrome

Biomarker Discovery and Validation for Fragile X Syndrome

With a $60,000 grant from FRAXA Research Foundation in 2015 that was renewed in 2016, Dr. Eric Klann of New York University will research biomarkers in fraile X syndrome and how to translate these markers from mouse models to human patients.

Read more

A Kinase Assay as a Biomarker for Fragile X Syndrome

A Kinase Assay as a Biomarker for Fragile X Syndrome
With a $90,000 grant from FRAXA Research Foundation over 2017-2018, Dr. Frank Kooy at the University of Antwerp, Belgium, is investigating whether phosphorylation abnormalities are a suitable biomarker for the Fragile X syndrome. $90,000 Grant Drs. Anke Van Dijck (FRAXA fellow, ganaxolone clinical trial), Ilse van der Werf, Geert Vandeweyer, Elisa Cappuyns (FRAXA fellow, this study), Frank Kooy R. Frank Kooy, PhD Principal Investigator University of Antwerp 2018 FRAXA Research Grant $90,000 over 2 Years “This Is Your Brain on Drugs” was a large-scale US anti-drugs TV campaign promoted by Partnership for a Drug-Free America in 1987. The purpose was to discourage use of illegal drugs by showing an egg frying in a pan simulating what drugs can due to your brain. It was incredibly simple and effective. TV Guide named it one of the top 100 commercials of all time. University of Antwerp researcher Frank Kooy, PhD, has a completely different updateRead more

MicroRNAs as Biomarkers in Fragile X Syndrome

MicroRNAs as Biomarkers in Fragile X Syndrome

With a $90,000 grant from FRAXA Research Foundation in 2015-2016, Dr. Mollie Meffert and Dr. Christina Timmerman at Johns Hopkins University studied groups of small RNAs, known as microRNAs, which are greatly decreased in brain tissue of Fragile X mice vs. normal controls.

Read more

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

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

With a $90,000 grant from FRAXA Research Foundation in 2016, 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.

Read more

Identifying Biomarkers for Fragile X Syndrome – A Study in Argentina

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. “Biomarkers are key to learning more about their correlation with clinical and behavioral characteristics across diverse developmental stages in Fragile X syndrome,” said Dr. Cogram, the principal investigator of FRAXA’s Drug Validation Initiative (FRAXA-DVI) to test preclinicaly potential compounds for FXS. “We are searching for biomarkers that could potentially be used for clinical trials for treatment in children, teenagers, and adults with Fragile X.” Cue parents. Yes, you. Targets: your Child’s Cognitive, Behavioral and Emotional Impairments Dr. Cogram and Dr. Carullo are looking for families of children withRead more

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

Targeting AMP-Activated Protein Kinase Pathway in Fragile X Syndrome

With a $100,000 grant from the FRAXA Research Foundation in 2015, Dr. Peter Vanderklish explored a novel strategy to treat Fragile X syndrome: AMPK activators. The good news is that there are FDA approved (for example, metformin) and naturally occurring AMPK activators (such as resveratrol, found in red wine).

Read more

Studies of Mega Green Tea Extract to Treat Fragile X Syndrome

Studies of Mega Green Tea Extract to Treat Fragile X Syndrome

With a $124,000 grant from the FRAXA Research Foundation from 2012-2014, Dr. Mara Dierssen and Dr. Rafael de la Torre conducted preclinical studies in Fragile X knockout mice and a clinical trial in Fragile X patients using Mega Green Tea Extract, which contains 45% by weight epigallocatechin gallate (EGCG).

Read more

Functional Interplay Between FMRP and CDK5 Signaling

Functional Interplay Between FMRP and CDK5 Signaling

With a $180,000 grant from the FRAXA Research Foundation over 2011-2014, Dr. Yue Feng and Dr. Wenqi Li at Emory University will study CDK5 pathway function and regulation in an effort to break down whether and how CDK5 signaling is affected by the loss of the Fragile X protein, FMRP, in the Fragile X mouse model.

Read more

Development of a Novel GABA-A Agonist in Fragile X Syndrome

Development of a Novel GABA-A Agonist in Fragile X Syndrome

Of the many genes known to be regulated by FMRP, the gamma-aminobutyric acid receptor A (GABA(A)), is gaining attention as a potential target for the treatment of FXS. Mounting evidence suggests decreased expression and functioning of GABA(A) is involved in the pathophysiology of FXS. Non-selective GABA(A) agonism in animal models of FXS has been associated with normalization of morphological features, GABA(A) expression, and behavior. However, the clinical use of these agents in Fragile X is associated with unwanted side-effects, such as sedation, dulling of cognition, and occasional paradoxical agitation, which limits their use. Given the limitations in available GABA(A)-based treatment of FXS, this group plans to investigate a novel selective GABA(A) agonist in a mouse model of FXS. This agent has the potential to relieve many symptoms of Fragile X without the unwanted side effects.

Read more

Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice

Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice

With a $90,000 grant from FRAXA Research Foundation over two years, Drs. Olivier Manzoni and Daniela Neuhofer researched the relationship between Fragile X syndrome and the areas of the brain that are involved in reward processing, regulation of emotional behavior and emotional memory as well as attention, planning and working memory.

Read more

Ab-Mediated Translation in Fragile X Syndrome

Ab-Mediated Translation in Fragile X Syndrome

With a $120,000 grant from FRAXA Research Foundation during 2011-2012, Dr. Cara Westmark at the University of Wisconsin explored the role of AbPP as a potential treatment option for fragile X. AbPP produces b-amyloid which is over-expressed in Alzheimer’s disease (AD) and Down syndrome. 

Read more

A Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse

A Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse

Dr. Davidovic has been examining changes in metabolism in various brain regions that are affected in Fragile X patients. She has defined a brain-specific metabolic signature of FXS and is testing treatment strategies to restore normal levels of these metabolites.

Read more

Clinical Trials Outcome Measures / Lithium Pilot Trial

Clinical Trials Outcome Measures / Lithium Pilot Trial

With a $281,824 grant from FRAXA Research Foundation from 2002-2011, Dr. Berry-Kravis at the Rush University Medical Center attempted to validate a new automated video tracking system for quantifying physical activity as an outcome measure for Fragile X clinical trials.

Read more