Test-Bed for Screening Drugs which Can Reactivate the FMR1 Gene

Test-Bed for Screening Drugs which Can Reactivate the FMR1 Gene

With $146,000 grant from FRAXA Research Foundation over 2012-2013, Drs. Anita Bhattacharyya and Xinyu Zhao at the University of Wisconsin developed a new mouse model of Fragile X syndrome which will enable testing of gene reactivation and gene therapy approaches to treatment. They transplanted human Fragile X neural cells differentiated from induced pluripotent stem cells into brains of neonatal mice and then testing for FMR1 reactivation. In 2015, The John Merck Fund assumed support for this work with a generous grant of $750,000 to the scientists. Results published.

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A Developmental Switch Exists in the Effects of FMRP

A Developmental Switch Exists in the Effects of FMRP
$90,000 FRAXA Research Grant for 2010-2011 With a $90,00 grant from FRAXA Research Foundation, Dr. Kimberly Huber and her team at the University of Texas at Southwestern found that there is a developmental switch of postsynaptic FMRP on synaptic function. This switch is controlled by MEF2 transcriptional activity. Kimberly Huber, PhD Principal Investigator Tong Zang, PhD FRAXA Postdoctoral Fellow University of Texas at Southwestern by Tong Zang, PhD Proper synapse maturation and elimination is crucial for the establishment of appropriate neural circuits that underlie sensory processing and cognition. Neuron of Fragile X patients as well as in the mouse model of Fragile X, Fmr1 KO mice, display more dendritic spines, the point of contact for excitatory synapses, as well as long and thin filopodia resembling immature spines. This suggests Fragile X mental retardation protein (FMRP) has a role in promoting synapse maturation and elimination. Altered regulation of these processes in FragileRead more

The miRNA Pathway in Fragile X Syndrome

With a $120,000 grant from FRAXA Research Foundation over 2008-2009, Drs. Oostra and deVrij at Erasmus University studied miRNA and Fragile X. miRNAs are RNAs that can repress the translation of target mRNAs – therefore they can play a role in protein synthesis within the neuron. Preliminary results showed large differences in miRNA expression in the Fragile X mouse brain compared to the wild type. This lab investigated the effect of mGluR5 antagonists on the levels of these specific miRNAs.

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Role of Matrix Metalloproteinases (MMP-9) 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.

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Pilot Trial of Minocycline in Fragile X

With a $40,000 grant from FRAXA, Dr. Carlo Paribello and his team at the Surrey Place Centre Fragile X clinic in Toronto, Ontario, ran an open label trial to see if minocycline can improve learning and reduce anxiety and behavioral problems in people with Fragile X. Twenty participants between the ages of 13 and 35 years take minocycline for two months.

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Clinical Trial of Aripiprazol in Fragile X Syndrome

Clinical Trial of Aripiprazol in Fragile X Syndrome

With a FRAXA Research Foundation grant of $30,000 in 2006, Dr. Erickson conducted a pilot clinical trial of an available medicine, aripiprazole (brand-name Abilify). This was an open-label 12-week trial in 12 people aged 6–25 years with Fragile X. Results were promising, and published: 10 of the 12 participants showed behavioral improvements.

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Taurine and Somatostatin as Potential Treatments for Fragile X Syndrome: A Unifying Neuro-Endocrine Hypothesis

With a $74,000 grant from FRAXA Research Foundation, Dr. Abdeslem El Idrissi at CUNY explored the GABA receptor system in Fragile X mice and tested somatostatin and taurine as potential therapies for Fragile X; while somatostatin must be infused intravenously, taurine is available as a nutritional supplement.

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Hypothalamic Pituitary Adrenal (HPA) Axis Dysregulation in Fragile X Syndrome

Hypothalamic Pituitary Adrenal (HPA) Axis Dysregulation in Fragile X Syndrome

The hypothalamic pituitary adrenal (HPA) axis is our central stress response system. FRAXA Research Foundation awarded Dr. Carolyn B. Smith $62,000 in funding in 2005 to explore the HPA axis in Fragile X mice. The results of their study indicate that, in FVB/NJ mice, the hormonal response to and recovery from acute stress is unaltered by the lack of Fragile X mental retardation protein. Results published.

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Role of Experience in Regulating Levels of the Fragile X Protein

Role of Experience in Regulating Levels of the Fragile X Protein

FRAXA Research Grant to Kenneth J. Mack, MD, PhD — Mayo Clinic with Peter K. Todd, MD, PhD, Postdoctoral Fellow   FRAXA Awards: $29,000 in 2001 $20,000 in 2000 Final Report on Dr. Mack’s Project While a professor at University of Wisconsin-Madison, Dr. Mack investigated whether and how FMRP levels are regulated in response to neuronal stimulation in vivo (in live animals). He looked at the effects of seizures and of experience in his experiments. Dr. Mack and colleagues published their findings in the Proceedings of the National Academy of Sciences: The Fragile X mental retardation protein is required for type-I metabotropic glutamate receptor-dependent translation of PSD-95 Peter K. Todd, Kenneth J. Mack, and James S. Malter PNAS | November 25, 2003 | vol. 100 | no. 24

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The Molecular Basis of Increased Seizure Severity in the Fragile X Knockout Mouse

With a $50,000 grant from FRAXA Research Foundation from 2002-2003, Dr. Carl Dobkin and his team at the New York Institute for Basic Research studied the causes for heightened seizure activity in Fragile X mice. Results published.

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