High MMP-9 activity levels in fragile X syndrome are lowered by minocycline.

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by lack of the FMR1 protein, FMRP, a translational repressor. Its absence leads to up-regulation of locally translated proteins involved in synaptic transmission and plasticity, including the matrix metalloproteinase-9 (MMP-9). In the Fmr1 knock-out (KO), a mouse model of FXS, an abnormal elevated expression of MMP-9 in the brain was pharmacologically down-regulated after treatment with the tetracycline derivative minocycline. Moreover, the rescue of immature dendritic spine morphology and a significant improvement of abnormal behavior were associated with down-regulation of MMP-9. Here, we report on high plasma activity of MMP-9 in individuals with FXS. In addition, we investigate MMP-9 changes in patients with FXS who have gone through a minocycline controlled clinical trial and correlate MMP-9 activity to clinical observations. The results of this study suggest that, in humans, activity levels of MMP-9 are lowered by minocycline and that, in some cases, changes in MMP-9 activity are positively associated with improvement based on clinical measures.

• Authors: Magdalena Dziembowska, Dalyir I Pretto, Aleksandra Janusz, Leszek Kaczmarek, Mary Jacena Leigh, Nielsen Gabriel, Blythe Durbin-Johnson, Randi J Hagerman, Flora Tassone
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 161A Issue 8 Pg. 1897-903 (Aug 2013) ISSN: 1552-4833 [Electronic] United States
• PMID: 23824974 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Chemical References

• Anti-Bacterial Agents
• Fragile X Mental Retardation Protein
• Matrix Metalloproteinase 9
• Minocycline

Topics

• Adolescent
• Animals
• Anti-Bacterial Agents (therapeutic use)
• Cells, Cultured
• Child
• Child, Preschool
• Cross-Over Studies
• Double-Blind Method
• Female
• Fragile X Mental Retardation Protein (blood)
• Fragile X Syndrome (blood, drug therapy, enzymology)
• Humans
• Matrix Metalloproteinase 9 (blood)
• Mice
• Minocycline (therapeutic use)
• Neurons (drug effects, metabolism, pathology)