Treatment Targets Archives • Page 5 of 7 • FRAXA Research Foundation

Fragile X Researcher, Cara Westmark, PhD

Ab-Mediated Translation in Fragile X Syndrome

September 13, 2012

This work found amyloid precursor protein (APP) overexpression and increased β-amyloid in Fragile X mice, implicating Alzheimer-related pathways in FXS pathology.

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.

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.

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.

Serotonergic Rescue of Synaptic Plasticity in FMR1 Knockout Mice

January 31, 2012

Dr. Zhu examined how serotonin-targeting drugs such as Buspar and Abilify influence synaptic plasticity, including LTP and LTD.

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.

Channelopathies: Altered Ion Channels in Fragile X Syndrome

September 15, 2011

Ion channel defects (“channelopathies”) in Fragile X disrupt neuron firing and network balance. This study maps these channel changes to guide targeted treatments.

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.

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.

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.

GABAergic Inhibitory Function in Fragile X Syndrome

February 1, 2011

Fragile X mice show weakened GABAergic inhibition in key brain regions like the amygdala. Enhancing GABA_A receptor activity reduced hyperactivity and improved inhibition.

Correcting Fragile X Syndrome by Inhibiting the Synaptic RNA-Binding Protein CPEB1

January 30, 2011

The Richter lab found that CPEB1 knockdown in Fmr1 KO mice normalized excessive protein synthesis and improved synaptic and memory problems tied to Fragile X.

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).

Reactivation of the FMR1 Gene

February 22, 2010

The team screened compounds with Neuropharm (UK) looking for compounds to reactivate the FMR1 gene. They also analyzed unmethylated full mutation cell lines.

Small Molecule Screen Using Fragile X Neural Stem Cells

February 1, 2010

Researchers found that FMRP-deficient neural stem cells divide too much and fail to mature properly; screening compounds revealed candidates restoring normal behavior.

Neuromotor Outcome Measures for Clinical Trials in Fragile X Syndrome

February 1, 2010

Drs. Nicole Tartaglia and Tracey Stackhouse advanced neuromotor testing for Fragile X, paving the way for better-targeted clinical trials.

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.

Stephen Haggarty, PhD, Harvard/MIT, Principal Investigator, FRAXA research grant

Small Molecule Modulators of Lithium for Treatment of Fragile X Syndrome

February 1, 2010

With a $219,500 FRAXA grant, Dr. Stephen Haggarty at Harvard/MIT used patient-derived stem cells to screen drugs targeting GSK3, aiming to enhance lithium therapy.

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.

Genome-wide Epigenetic Markers in Fragile X

February 5, 2009

Dr. Miklos Toth’s FRAXA-funded work at Cornell University examined how epigenetic factors shape the severity of Fragile X symptoms.

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.