Mechanisms of Tolerance to Chronic mGluR5 Inhibition

Mechanisms of Tolerance to Chronic mGluR5 Inhibition

Over the past few years, both Novartis and Roche sponsored large-scale clinical trials of metabotropic glutamate receptor 5 (mGlu5) negative allosteric modulators (NAMs) to treat Fragile X syndrome (FXS). With a $90,000 grant from FRAXA Research Foundation in 2015-2017, Dr. Mark Bear’s team will explore if mGlu5 NAMs dosed chronically causes tolerance, and if so, how it develops and to probe new avenues to prevent or circumvent it.

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Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome

Enhancement of NMDA Receptor Signaling for the Treatment of Fragile X Syndrome
FRAXA Research Foundation funded a 2016-2017 Fellowship for Dr. Stephanie Barnes in the University of Edinburgh lab of Dr. Emily Osterweil. With this $90,000 award, the team is investigating NMDA signaling in fragile X syndrome mice. $90,000 GrantEmily Osterweil, PhD Principal Investigator Stephanie Barnes, PhD FRAXA Postdoctoral Fellow University of Edinburgh 2016-2017 FRAXA Research Grant $90,000 over 2 Years A Neuron to Remember: Correcting Imbalances in Fragile X SyndromeUniversity of Edinburgh Researcher Emily Osterweil, PhD, Probes the Brain’s Biochemistry to Correct Imbalances We know the “X” in Fragile X refers to the X chromosome, but it could just as easily refer to the unknown.Such as why do people with Fragile X have an excessive production of new proteins in their brains that lead to imbalances? That question is being dissected in the lab of Emily Osterweil, PhD, chancellor’s fellow, Centre for Integrative Physiology, University of Edinburgh, UK. Dr. Osterweil is usingRead more

Lovastatin Discovery in Fragile X Mice Leads FRAXA to Fund Clinical Trials

Lovastatin Discovery in Fragile X Mice Leads FRAXA to Fund Clinical Trials
Available Medication Lovastatin Corrects Excess Protein Synthesis in Fragile X Mice Dr. Emily Osterweil At the opening dinner of the 2011 FRAXA Investigators Meeting in Southbridge, MA,  Dr. Emily Osterweil was awarded the FRAXA Pioneer Award for work demonstrating that Lovastatin could treat Fragile X.  Dr. Osterweil conducted her experiments in the MIT laboratory of Dr. Mark Bear; she has since established her own laboratory at the University of Edinburgh. The team discovered that lovastatin, a drug widely prescribed for high cholesterol, can correct excess hippocampal protein synthesis in the mouse model of FXS and can prevent epileptogenesis. The work is published in the prestigious neuroscience journal Neuron: Lovastatin Corrects Excess Protein Synthesis and Prevents Epileptogenesis in a Mouse Model of Fragile X Syndrome. One implication of the mGluR theory of Fragile X is that there are exaggerated consequences of activation of signaling pathways which link metabotropic glutamate receptors (mGluRs) to the cellular machinery ofRead more