The Slack Potassium Ion channel is a Therapeutic Target for Fragile X
With $282,000 in funding from FRAXA Research Foundation, Dr. Leonard Kaczmarek and colleagues explored association of Slack channels with the Fragile X protein (FMRP).
Pilot Clinical Trial of Lithium in Fragile X Shows Promising Results
With $65K from FRAXA, Dr. Berry-Kravis at Rush University ran a pilot lithium trial in 15 Fragile X patients. Results published.
Encouraging Results from First Trial of Minocycline in Fragile X
A clinical trial of minocycline in children with Fragile X found significantly better global improvement vs. placebo, supporting its safety and potential.
Reactivation of the FMR1 Gene
The team screened compounds with Neuropharm (UK) looking for compounds to reactivate the FMR1 gene. They also analyzed unmethylated full mutation cell lines.
Small Molecule Screen Using Fragile X Neural Stem Cells
Researchers found that FMRP-deficient neural stem cells divide too much and fail to mature properly; screening compounds revealed candidates restoring normal behavior.
Neuromotor Outcome Measures for Clinical Trials in Fragile X Syndrome
Drs. Nicole Tartaglia and Tracey Stackhouse advanced neuromotor testing for Fragile X, paving the way for better-targeted clinical trials.
The Role of FMRP and Small, Non-Coding RNAs in Translation
Drs. Henri Tiedge and Jun Zhong investigated how BC1 RNA could restore balance in Fragile X brains, pointing toward RNA-targeted treatments.
Small Molecule Modulators of Lithium for Treatment of Fragile X Syndrome
With a $219,500 grant from FRAXA Research Foundation, Dr. Stephen Haggarty from Havard/MIT developed a high-throughput drug screen to find compounds that inhibit GSK3, a critical enzyme in Fragile X. He looked for compounds that can accomplish this either alone or in combination with lithium, offering the possibility of enhancing the effectiveness of lithium as a treatment. His drug screen used patient-specific neural progenitor (NP) cells derived from human induced pluripotent stem cells (iPSCs) – which are created from cells in a skin biopsy from people with Fragile X syndrome (FXS) and other autism spectrum disorders.
Aberrant Behavior Checklist in Fragile X Syndrome
With a $10,000 grant from FRAXA Research Foundation, Dr. Hessl at the University of California at Davis led a collaborative study to analyze the Aberrant Behavior Checklist (ABC) as an outcome measure for children and adults with Fragile X syndrome. Results published.
Composition and Localization of Dendritic mRNAs in Fragile X Syndrome
With a $80,000 grant from FRAXA Research Foundation over 2 years, Drs. Smith and Wang are investigating which proteins, as well as the mRNA’s that code those proteins, are dysregulated in Fragile X. They have developed a elegant system to visualize the proteins and mRNA’s and determine where they are spacially in the neuron. This will help to better understand the root causes of Fragile X syndrome and to design targeted treatments.
Role of the Cerebellum in the Dysfunction of Fragile X Syndrome
With FRAXA funding, Dr. Ben Oostra’s Dutch-Belgian team linked Fragile X to cerebellar motor learning deficits. Results published in Neuron (2008).
Developing Fragile X Treatments in Fruit Flies and Mice
FRAXA’s $380K grant supported Drs. McBride, Jongens, and Choi in validating Fragile X treatments in mice to prepare for trials. Findings published.
Imaging Synaptic Structure and Function in Fragile X Mice
With $150K from FRAXA, Dr. Carlos Portera-Cailliau studied Fragile X mouse brains to examine dendrite structure and mGluR5 treatment effects.
Genome-wide Epigenetic Markers in Fragile X
With $45,000 in grants from FRAXA Research Foundation over several years, Dr. Miklos Toth of Cornell University studied epigenetics (ie factors other than the gene itself) which can determine symptom severity in Fragile X.
Mouse Models of Fragile X Syndrome
With FRAXA support, Dr. Oostra’s team built the first Fragile X mouse model and published pivotal studies advancing the field.
Role of Matrix Metalloproteinases (MMP-9) in Fragile X
With a $220,000 grant from FRAXA Research Foundation over 3 years, Dr. Iryna Ethell from the University of California at Riverside studied the regulation of dendritic structure by matrix metalloproteinases and other extracellular signaling pathways. This work identified a major treatment strategy for Fragile X with the available MMP-9 inhibitor, minocycline.
Novel Functions of Drosophila FMRP
With a $120,000 grant from FRAXA Research Foundation over 2 years, Dr. Thomas Dockendorff from the University of Tennessee and his colleagues were pioneers in using the power of fly genetics to understand the different functions of the fly version of the Fragile X protein.
Basic Mechanisms of Disease and Potential Therapeutic Strategies
Dr. Stephen Warren’s FRAXA-funded research at Emory led to the Fragile X gene discovery and new breakthroughs using stem cells and model systems.
Role of FMRP in the Regulation of Synaptic Plasticity
FRAXA’s $1M support helped Drs. Greenough and Weiler reveal FMRP’s role at synapses, shaping today’s understanding of Fragile X syndrome.
Altered Cyclic AMP Signaling in Fragile X
With $125,000 grant from FRAXA Research Foundation over 2006-2008, Dr. Anita Bhattacharyya at the University of Wisconsin Waisman Center investigated abnormalities in cyclic AMP signaling in Fragile X syndrome. Results published.
Glutamate Metabolism in Fragile X Mouse Brain
With a $95,000 grant from FRAXA Research Foundation over 2 years, Mary McKenna at the University of Maryland studied the role of metabotropic glutamate receptors (mGluR) and how they affect other cells and pathways.
Using Fenobam to Reduce APP and Abeta in Fragile X Mice
With a $130,000 grant from FRAXA Research Foundation over 2008-2009, Drs. James Malter and Cara Westmark at the University of Wisconsin studied the relationship between the Fragile X protein FMRP and APP, a protein important to the pathology of Alzheimer’s Disease. APP may also contribute to the pathology of Fragile X, and its major metabolite, Aß, may contribute to abnormal protein synthesis via a positive feedback loop. This project sought to restore normal dendritic protein synthesis in Fragile X mice by breaking into this loop.
In Vivo Imaging of Synaptic Abnormalities in a Mouse Model of Fragile X Syndrome
With an $85,000 grant from FRAXA Research Foundation over 2007-2008, Dr. Wen-Biao Gan and his team at New York University studied in-vivo protein development using imaging in mouse models to determine when pre- and postsynaptic structural plasticity occurs to target and when it develops abnormally.
Sleep and Circadian Rhythms in Fragile X Mutant Drosophila
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.