Repurposing FDA-Approved Drugs to Treat Major Depressive Disorder in Fragile X

Kimberly F. Raab-Graham, PhD
Principal Investigator

Chelcie F. Heaney, PhD
Co-Principal Investigator

Wake Forest School of Medicine
Winston Salem, North Carolina

2021 Grant Funding: $90,000

University Total Funding: $90,000

Summary

Did you know that depression is more common in those with autism and/or Fragile X?

Even more disturbing is the discovery that current treatments for depression do not work in Fragile X mice. These researchers published a study showing that standard treatments for depression need the protein FMRP to work — and people with Fragile X syndrome have little or no FMRP.

With this grant, the team will work to develop a rapid screening tool to identify FDA-approved drugs which can treat depression in people with Fragile X syndrome.

The Science

By Kimberly F. Raab-Graham, PhD

People with Autism Spectrum Disorder (ASD) have an increased risk of developing Major Depressive Disorder (MDD) by the time they are 30 years old compared to people without ASD. Fragile X syndrome (FXS) is the single leading genetic cause of ASD, and caretakers report mood and depression as priorities for treatment development. FXS results from the functional loss of the gene FMR1; this loss prevents expression of the Fragile X Mental Retardation Protein (FMRP). Importantly, people with MDD and those with ASD have less FMRP expression.

Our recent experiments show that current treatments for MDD are ineffective in a standard preclinical mouse model for FXS, which indicates that these treatments need the protein FMRP to work. This proposal builds upon our published work that identifies how antidepressants induce FMRP-dependent changes that increase the number of connections and strengthen communication between brain cells. Using a computational approach that predicts how to increase these connections in the absence of FMRP, we will identify FDA-approved drugs to test as potential antidepressants in a preclinical model of FXS.

These studies aim to develop a rapid screening process for therapeutics with the potential for repurposing. This rapid screening process will decrease the amount of time it takes for a drug to go from bench-to-bedside. The proposed studies develop a highly innovative and novel approach to address the need for effective treatments of MDD in people with FXS.

Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Explore Current Research Grants
Help Fund the Cure

Global Leader in Fragile X Research

FRAXA-funded researchers around the world are leading the way towards effective treatments and ultimately a cure.

Explore Current Research Grants
Help Fund the Cure

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