# Translational medicine and mechanistic studies of brain neurophysiology in Fragile X Syndrome

> **NIH NIH U54** · CINCINNATI CHILDRENS HOSP MED CTR · 2020 · $1,600,000

## Abstract

Over the last six years our project teams have demonstrated that neurophysiology abnormalities
are conserved across mice and humans in fragile X syndrome (FXS). These findings across
species provide a great opportunity to advance mechanistic understanding of clinically relevant
illness features and develop translational biomarkers and aid treatment discovery. These
advances can bridge the significant chasm between preclinical and clinical success in new
treatment development. We take mechanistic approaches to determining the drivers of
neurophysiology dysregulation across three integrated projects spanning human, in vivo, and ex
vivo mouse study. This allows for levels of analysis from whole brain network modeling to
microcircuit and molecular analysis to aid target discovery while improving translational
medicine efforts in FXS. In doing this we place emphasis on recognizing heterogeneity within
FXS and using this understanding to model how to best interpret and link preclinical and clinical
study. Out of this appreciation of the challenges to translational efforts in our field, we have
developed a synchronized approach to the analysis and interpretation of neurophysiology data
ensuring comparable results across research platforms. The striking consistency of findings
across levels of investigation and species offers an unprecedented opportunity to investigate
mechanisms of brain dysfunction across mouse and human study thus significantly improving
opportunities for translational medicine development in FXS- a multidisciplinary mission that is
ideal for a Center environment. Project 1 (Erickson/Sweeney; Cincinnati) will conduct human
FXS neurophysiology, behavior, and pharmacological probe studies to pursue advanced
neurophysiology modeling of cortical hyperexcitability and abnormal response to stimuli while
also seeking to resolve heterogeneity across FXS in humans. Project 2 (Binder/Razak;
Riverside) will develop translational neurophysiological biomarkers for FXS in the Fmr1 KO
mouse using both surface and depth multi-electrode array technology. Project 3 (Huber/Gibson,
UTSW) will investigate the microcircuit and molecular mechanisms of neurophysiologic
dysregulation in the Fmr1 KO mouse. All Projects will examine candidate mechanisms of
neurophysiologic dysregulation with a pharmacological probe strategy to test mechanisms of
interest in parallel studies of mice and patients.

## Key facts

- **NIH application ID:** 10156166
- **Project number:** 1U54HD104461-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Craig Erickson
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,600,000
- **Award type:** 1
- **Project period:** 2020-09-25 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156166

## Citation

> US National Institutes of Health, RePORTER application 10156166, Translational medicine and mechanistic studies of brain neurophysiology in Fragile X Syndrome (1U54HD104461-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10156166. Licensed CC0.

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