mGluR Archives • Page 2 of 3 • FRAXA Research Foundation

Seizures in Fragile X Syndrome and Therapeutic Potential of NMDA Receptor Antagonists

September 8, 2014

Dr. Wong studies how NMDA and mGluR receptors interact to trigger seizures in Fragile X, revealing NR2B-specific blockers as a promising targeted treatment.

Why Did Fragile X Clinical Trials of mGluR Antagonists Fail?

August 15, 2014

by Michael Tranfaglia, MD. In my opinion, the Fragile X clinical trials of AFQ056 sponsored by Novartis failed because of a dose range that was inadequate for Fragile X, and because of the unexpected development of tolerance.

Translation-Independent Functions of FMRP in Excitability, Synaptic Transmission and Plasticity

September 12, 2013

Study pinpointed presynaptic calcium dysfunction as the driver of STP defects in Fragile X, and BK channel activation restored normal synaptic signaling.

The mTOR Pathway in Fragile X Syndrome

September 6, 2013

FRAXA-funded research showed that blocking S6K1 in Fragile X mice improves social, behavioral, and physical symptoms.

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

June 11, 2013

FRAXA honored Dr. Emily Osterweil for discovering that lovastatin can correct key Fragile X abnormalities. Her findings were published in Neuron.

Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice

June 2, 2013

FRAXA-funded studies found faulty endocannabinoid signaling in Fragile X brain circuits for reward and emotion, and boosting 2-AG restored normal function.

Kimberly Huber, Ph.D., FRAXA Investigator

Targeting mGluR-LTD to Treat Fragile X Syndrome

March 12, 2013

With FRAXA support, Dr. Kimberly Huber uncovered how mGluR signaling contributes to Fragile X, laying the foundation for major clinical advances.

Preclinical Evaluation of Serotonin Receptor Agonists as Novel Pharmacological Tools in Fragile X Syndrome

February 22, 2013

With FRAXA funding the team found that activating 5-HT7 receptors reversed excess mGluR-LTD in Fragile X mice, pointing to a new route to fix synapses.

Small Rho GTPases, a Potential Therapeutic Target for Fragile X Syndrome

January 30, 2013

Dr. MariVi Tejada from the University of Houston tested several potential therapeutic compounds in an attempt to rescue function in the mouse model of Fragile X.

Evaluation of CamKII Dependent Regulation of mGluR5-Homer Scaffolds as a Potential Therapeutic for Fragile X Syndrome

January 30, 2013

Disrupted mGluR5–Homer scaffolding in Fragile X is linked to excess CaMKII activity. Restoring this interaction could rebalance signaling and improve symptoms.

Synaptic Actin Signaling Pathways in Fragile X

September 11, 2012

Fragile X neurons show excess or mis-timed actin remodeling at synapses caused by FMRP loss. Modulating actin regulators rescued connectivity in mice.

Compound that Inhibits mGluR5 Corrects Signs of Fragile X in Adult Mice

April 13, 2012

A Roche and MIT study published in Neuron finds that an mGlu5 inhibitor, CTEP, can reverse many Fragile X symptoms in adult mice.

Role of JNK in FMRP Regulated Translation in Fragile X Syndrome

January 31, 2012

JNK kinase is abnormally active in Fragile X model mice and directly regulates mGluR-dependent translation of FMRP targets, pointing to JNK as a therapeutic target.

Efficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila

January 30, 2012

Using a fruit-fly Fragile X model, researchers screened many drugs quickly to find those that improve behavior, speeding up potential treatment testing.

Role of Excessive Protein Synthesis in the Ontogeny of FXS

May 8, 2011

Excessive neuronal protein synthesis is not just a symptom but appears to cause early synaptic wiring defects in Fragile X — highlighting translation control as a key target.

Manipulating Basal and mGluR-Stimulated cAMP Level in FXS Model Mice

February 1, 2011

Fragile X mice show reduced basal cAMP and exaggerated mGluR-LTD; boosting cAMP or blocking specific adenylyl cyclases rescues synaptic and behavioral defects.

The Slack Potassium Ion channel is a Therapeutic Target for Fragile X

January 7, 2011

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).

The Role of FMRP and Small, Non-Coding RNAs in Translation

February 1, 2010

Drs. Henri Tiedge and Jun Zhong investigated how BC1 RNA could restore balance in Fragile X brains, pointing toward RNA-targeted treatments.

Sean McBride, PhD, Albert Einstein College of Medicine, FRAZA research grant

Developing Fragile X Treatments in Fruit Flies and Mice

February 26, 2009

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

February 5, 2009

With $150K from FRAXA, Dr. Carlos Portera-Cailliau studied Fragile X mouse brains to examine dendrite structure and mGluR5 treatment effects.

Iryna Ethell, PhD, at University of California

Role of Matrix Metalloproteinases (MMP-9) in Fragile X

February 2, 2009

With a $220,000 FRAXA grant, Dr. Iryna Ethell’s team at UC Riverside uncovered MMP-9’s role in Fragile X—leading to a major treatment strategy using minocycline.