Altered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome
With a $106,800 grant from FRAXA Research Foundation over 2 years, Drs. Stephan Kindler and Hans-Jurgen Kreieinkamp studied a protein, Shank1, which is overabundant in Fragile X syndrome.
Manipulating Basal and mGluR-Stimulated cAMP Level in FXS Model Mice
With a $90,000 grant from FRAXA Research Foundation, Dr. Hongbing Wang’s team from Michigan State University looked at a treatment target “downstream” of the mGluR5 called cyclic AMP (cAMP). Levels of cAMP are lower in FXS patients and animal models, suggesting that it plays a role in FXS. Drugs that raise levels of cAMP may effectively treat Fragile X. We are very pleased to report that, in 2012, Dr. Wang received a 5-year, $250,000 per year R01 grant from NIH to continue this promising research.
Correcting Fragile X Syndrome by Inhibiting the Synaptic RNA-Binding Protein CPEB1
The Richter lab is the foremost research group in the world in the study of CPEB, a protein critical for regulation of protein synthesis. With $170,000 in grants from FRAXA Research Foundation over 2008-2011, Dr. Joel Richter of the University of MA Medical School explored whether inhibitions of the CPEB may be a viable approach for treatment of Fragile X.
Reactivation of the FMR1 Gene
With a $50,000 grant from FRAXA Research Foundation, Dr. Giovanni Neri and his team at Universita Cattolica del S. Cuore screened compounds with Neuropharm (UK) for reactivating compounds. This team is collaborating with Dr. Stephen Haggarty at Harvard and MIT (who also has a FRAXA grant), researching reactivation of the FMR1 gene and characterization of cell lines with unmethylated full mutations. Results published.
Role of the Cerebellum in the Dysfunction of Fragile X Syndrome
Correcting Fragile X Syndrome Deficits by Targeting Neonatal PKCε Signaling in the Brain Ben A. Oostra, PhD Principal Investigator Erasmus University Rotterdam, The Netherlands 2004-2005 Grant Funding: $119,000 Summary The Dutch-Belgian Fragile X Consortium led by Dr. Oostra created the first Fragile X mouse model – the FMR1 knockout mouse – and went on to…
Developing Fragile X Treatments in Fruit Flies and Mice
With a $380,000 grant from FRAXA Research Foundation from 2005-2009, Drs. Sean McBride, Tom Jogens, and Catherine Choi studied one of the most important aspects of FRAXA’s research; the preclinical validation of potential therapeutic strategies. Many labs have found new leads for treatment. However, very few have the capacity to test new drugs in the mouse model to establish efficacy rigorously enough to lead to clinical trials. The McBride lab (in a broad collaboration with the Choi, Jongens, and Skoulakis groups) aims to do just that. Results published.
Imaging Synaptic Structure and Function in Fragile X Mice
FRAXA Research Foundation grants $150,000 over 2005-2009 to Dr. Carlos Portera-Cailliau to study intact, anesthetized Fragile X mouse brains, looking for defects in the density, length, or dynamics of the dendrites. They looked for changes in the neurons after treatment with mGluR5 antagonists.
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.
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
With $245,000 in grants from FRAXA Research Foundation, Dr. Stephen Warren and his lab at Emory University studied all aspects of Fragile X syndrome, from the mechanisms of repeat expansion to high-throughput drug screens in the Drosophila model of Fragile X. The Warren lab made the original discovery of the Fragile X gene, FMR1, in collaboration with the Nelson and Oostra labs, and is recognized internationally as a leader in molecular genetics. Recent projects include establishment of induced pluripotent stem cell lines from Fragile X patients, and determination of other forms of mutation in the Fragile X gene, other than the most common trinucleotide repeat expansion.
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.
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.
AMPAkines and BDNF in Fragile X: UCI Researchers Restore Memory Process in Fragile X
With a $104,498 grant from FRAXA Research Foundation from 2003-2008, Dr. Julie Lauterborn at the University of California has done several studies on dentritic spines and finding treatment targets for memory retention in Fragile X mice.
Development of the Fragile X Brain: Cellular Processes Regulated by FMRP During Development
With a $120,000 grant from FRAXA Research Foundation over 2 years, Dr. Peter Kind and his team at the University of Edinburgh will study the way FMRP affects and is affected by cortical development.
Targeting the Role of Group 1 Metabotropic Glutamate Receptors
With a $40,000 grant from FRAXA Research Foundation in 2008, Dr. Huibert Mansvelder and his team at the University of Amsterdam studied the role of different receptors and their reactions to drug compounds.
Effects of Alternative Splicing at FMR1 Exon 15 on Understanding Fragile X Syndrome
With a $118,500 grant from FRAXA Research Foundation from 2007-2008, Dr. Robert Denman and his team at the New York State Institute for Basic Research studied protein splicing, specifically looking at exon 15-encoded residues of of FMPR.
Molecular Basis of Fragile X Syndrome: Genetic Modeling in Zebrafish
With a $52,500 grant from FRAXA Research Foundation in 2008, Dr. Robert Richards and his team from the University of Adelaide studied zebrafish models and embryo development abnormalities to search for treatment targets.
In Vitro Reactivation of the Fragile X Gene
With a $60,000 grant from FRAXA Research Foundation, Dr. Giovanni Neri and his team at Universita Cattolica del S. Cuore explored reactivation of the FMR1 gene and characterization of cell lines with unmethylated full mutation.
FMRP-MAP1b RNA Interactions in Fragile X Syndrome
With a $95,000 grant from FRAXA Research Foundation from 2006-2007, Dr. Mihaela Mihailescu and her team at Dusquesne University studied the relationship between FMRP, RNA sequences, and G quartet structure. Results published.
Regulation of Group I Metabotropic Glutamate Receptor Trafficking in Fragile X
With an $83,500 grant from FRAXA Research Foundation in 2005 and 2007, Dr. Anna Fracesconi at Albert Einstein College studied the patterns and pathways of different receptors related to Fragile X.
Decreased Excitatory Drive onto Parvalbumin-Positive Neocortical Inhibitory Neurons in a Mouse Model of Fragile X Syndrome
With an $80,000 grant from FRAXA Research Foundation over 2006-7, Drs. Jay Gibson and Kimberly Huber at the University of Texas at Southwestern examined if the defected inhibitory neurotransmission was a primary or secondary symptom of Fragile X to determine where future treatment targets should be focused.