Reactivating the FMR1 Gene to Reverse Fragile X Syndrome

Reactivating the FMR1 Gene to Reverse Fragile X Syndrome

Jeannie Lee, MD, PhD
Principal Investigator
Hungoo Lee, PhD
FRAXA Fellow
Massachusetts General Hospital
Boston, MA
2019-2022 Grant Funding: $140,000
With support from The Pierce Family Fragile X Foundation

Summary

FRAXA has awarded $140,000 to Dr. Jeannie Lee and Dr. Hungoo Lee at Harvard Medical School and Massachusetts General Hospital. This team is targeting the root cause of Fragile X syndrome: a silenced single gene, called FMR1.

With a previous $180,000 grant from FRAXA Research Foundation and The Pierce Family Fragile X Foundation from 2016-2018, the team ran a series of studies aimed at reactivating FMR1. They found a method using combinations of drugs which spur the gene to produce its normal protein product. Using drug “cocktails” they are able to reactivate FMR1 in cells in their lab! Dr. Lee explains in this video.

The Science

by Jeannie Lee, MD, PhD and Hungoo Lee, PhD

We have found an exciting new methodology to reactivate the FMR1 gene in Fragile X syndrome (FXS) patient-derived human pluripotent stem cells (hPSCs). Our method involves treating cells with kinase inhibitors (drugs) that surprisingly leads to epigenetic modification of the trinucleotide repeat region that causes FXS.

In patient-specific cells, the treatment unsilences the FMR1 gene and results in full restoration of FMRP, the protein required for synaptic regulation, which is lacking in FXS. Our method is therefore a potential disease-specific treatment or cure for FXS.

With the current grant, we will:

  1. Optimize the composition of the reactivating cocktail.
  2. Test efficacy in neuronal cells from FXS patient iPSCs.
  3. Investigate the underlying mechanism to better define the reactivation process.

Grant Post Revisions

  • 2022/09 - Research grant renewed, The Science updated.
  • 2019/07 - Original grant post published.

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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