Targeted Transcriptional Reactivation of FMR1 in Fragile X Syndrome Stem Cells
Peter Todd, MD, PhD
Principal Investigator
Jill Haenfler, PhD
FRAXA Fellow
University of Michigan
Ann Arbor, MI
2016-2017 Grant Funding: $90,000
Summary
University of Michigan researcher Peter Todd, MD, PhD, is using CRISPR to selectively turn the Fragile X gene back on in cells
The Results
Results Published in Front Mol Neurosci. 2018 Aug 15
Targeted Reactivation of FMR1 Transcription in Fragile X Syndrome Embryonic Stem Cells
See Also:
How Promising is CRISPR for Fragile X? An Interview with Dr. Peter Todd
The Science
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.
