behavior Archives • Page 8 of 10 • FRAXA Research Foundation

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.

Fragile X Clinical Trial: Novartis Trial Results Are In, and They’re Not Pretty

June 26, 2014

This year’s Gordon Conference just finished, and Novartis presented their results. To say that the trial results for AFQ056 were disappointing would be the understatement of the century!

Novartis Discontinues Development of mavoglurant (AFQ056) for Fragile X Syndrome

April 24, 2014

Mavoglurant trials in Fragile X did not show improvement vs. placebo, leading Novartis to end the program and wind down the open-label extension.

Social Behavior as an Outcome Measure for Fragile X Clinical Trials

September 13, 2013

FRAXA funding helped identify reliable social behavior tests in Fragile X mice and showed an mGluR5 treatment could improve sociability, guiding future trials.

Glycogen Synthase Kinase-3 (GSK3), Lithium and Fragile X

September 12, 2013

Dr. Jope found that lithium (at usual therapeutic doses) and investigational GSK3 inhibitors can reverse a number of cognitive deficits in FMR1 knockout mice.

Development of a Novel GABA-A Agonist in Fragile X Syndrome

September 9, 2013

FRAXA funded analysis of a selective GABA-A drug for Fragile X, leading to a clinical trial at Cincinnati Children’s to test this potential treatment.

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.

Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

September 2, 2013

Dr. Broadie showed that MMP enzymes disrupt synapse development in Fragile X. MMP inhibitors (e.g. minocycline) improved connectivity and behavior in fruit flies.

Dysruption of Endocannabinoid Mediated Synaptic Plasticity in the Nac of FMR1 Null Mice

June 10, 2013

This team was able to establish the endocannabinoid system as a therapeutic target for Fragile X syndrome. They also showed that the system can be targeted with pharmacology.

Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

June 2, 2013

With FRAXA funding, Dr. Khaleel Razak and Dr. Iryna Ethell explored robust biomarkers relevant to the FXS and the efficacy of minocycline treatment.

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.

Treatment of Fragile X Syndrome via Dopamine Enhancers and Glutamate Inhibitors

June 2, 2013

In Fragile X mice, low dopamine signaling and excessive glutamate activity were targeted with dual therapy: dopamine enhancers plus glutamate inhibitors.

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.

Clinical Trials FAQ ← Frequently Asked Questions

January 11, 2013

Wondering which Fragile X trial is right? Eligibility varies, so most families qualify for just one. Talk with your closest clinic to find the best fit.

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.

Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value

September 2, 2012

Targeting the PI3K/mTOR cascade — specifically p110β — in Fragile X mice reversed neural and behavioral dysfunctions, validating it as a treatment pathway.

Reward Function in Fragile X Syndrome

September 2, 2012

Loss of FMRP disrupts dopamine-driven reward function—Fragile X mice show impaired cocaine sensitization and place preference, revealing new plasticity defects.

A Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse

September 1, 2012

This work revealed small-molecule metabolic changes in Fragile X brains and is using them to build a drug-efficacy index for screening therapies.

Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice

August 22, 2012

Researchers found that Fragile X brain circuits show faulty ion channel activity (channelopathies). Fixing these channels may restore normal brain signalling.

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.

In Vitro Coherent Network Activity

February 22, 2012

This work revealed that Fragile X neurons form disordered network dynamics—laying groundwork for using network activity as a treatment-screening metric.

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.

Altered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome

April 30, 2011

Loss of FMRP leads to excess synthesis of the scaffold protein Shank1 at dendrites. Elevated Shank1 may impair synaptic pruning and drive Fragile X spine pathology.

Why Did Fragile X Clinical Trials of mGluR Antagonists Fail?

Fragile X Clinical Trial: Novartis Trial Results Are In, and They’re Not Pretty

Novartis Discontinues Development of mavoglurant (AFQ056) for Fragile X Syndrome

Social Behavior as an Outcome Measure for Fragile X Clinical Trials

Glycogen Synthase Kinase-3 (GSK3), Lithium and Fragile X

Development of a Novel GABA-A Agonist in Fragile X Syndrome

The mTOR Pathway in Fragile X Syndrome

Matrix Metalloproteinase Therapeutic Treatments for Fragile X Syndrome

Dysruption of Endocannabinoid Mediated Synaptic Plasticity in the Nac of FMR1 Null Mice

Effects of minocycline on vocal production and auditory processing in a mouse model of Fragile X

Endocannabinoid Mediated Synaptic Plasticity in Fragile X Mice

Treatment of Fragile X Syndrome via Dopamine Enhancers and Glutamate Inhibitors

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

Clinical Trials FAQ ← Frequently Asked Questions

Synaptic Actin Signaling Pathways in Fragile X

Genetic and Pharmacologic Manipulation of PI3K Activity in FXS: Assessing Potential Therapeutic Value

Reward Function in Fragile X Syndrome

A Metabolomic Drug Efficacy Index to Test Treatments in the Fragile X Mouse

Inherited Channelopathies in Cortical Circuits of Fmr1 KO Mice

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

In Vitro Coherent Network Activity

Role of JNK in FMRP Regulated Translation in Fragile X Syndrome

Efficient Screening for Pharmaceutical Amelioration of FXS Behavioral Deficits in Drosophila

Altered Dendritic Synthesis of Postsynaptic Scaffold Protein Shank1 in Fragile X Syndrome

Support FRAXA

Get In Touch!

Explore Fragile X & Research

Get FRAXA Updates