Targeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells

With a grant from FRAXA Research Foundation awarded in 2016, University of Michigan researcher Peter Todd, MD, PhD, is using CRISPR to selectively turn the fragile X gene back on in cells

Dr. Peter Todd
$90,000 Grant
Peter Todd, MD, PhD
Principal Investigator

Jill Haenfler, PhD
FRAXA Postdoctoral Fellow

University of Michigan
2016-2017 FRAXA Research Grant
$90,000 over 2 Years
Funded with Support from the Klebe and Samuelson Families

This team’s central hypothesis is that effective treatments for fragile X syndrome must directly target the underlying cause of the disease: silencing of the FMR1 gene. They will utilize novel approaches including CRISPR to reactivate the gene, with an aim of achieving a breakthrough in Fragile X research.

Until recently, it was thought that most fragile X syndrome patients exhibited complete methylation and thus no FMR1 mRNA transcription. However, new studies reveal that a significant fraction of FXS cases show incomplete FMR1 methylation and continued FMR1 transcription. The degree of methylation exhibited correlates with FMR1 expression levels and impacts symptom severity. These results suggest that even small changes in FMRP expression might lead to marked improvements.

The goal of this project is to develop methods for augmenting transcription of the FMR1 gene.