Rockefeller University: Potential new treatment for Fragile X targets one gene to affect many

Above: Mouse brains with Fragile X Syndrome (lower) lose the ability to regulate proteins like Brd4 (green). Photo from The Rockefeller University.

A new publication in the journal Cell describes efforts by two groups at Rockefeller University to understand effects of absence of FMRP on a group of the ~1000 mRNA targets that encode proteins that regulate expression of other genes.

We know that nearly all cases of fragile X syndrome result from absence of the protein product of the FMR1 gene, FMRP. FMRP functions to regulate production of select proteins in cells by interacting with messenger molecules (mRNAs) that encode their production. Research into the mechanisms of fragile X syndrome has focused on understanding which mRNAs are FMRP targets, and how the absence of FMRP changes their functions.

In the new research from Rockefeller University, the groups found that absence of FMRP results in increases in the BRD4 gene product, which regulates expression of a large network of other genes, some of which are involved in nerve cell functions that are impaired in fragile X syndrome. Using an inhibitor of BRD4, they could correct some of the defects in the mouse model of FMRP deficiency, suggesting a new path toward therapy through inhibiting the action of this class of protein.

Read more at Rockefeller University’s website.

Explanation provided by David L. Nelson, PhD, Editor at American Journal of Human Genetics, Cullen Foundation Professor at Depart of Molecular and Human Genetics Baylor College of Medicine.