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

Am J Med Genet A. 2013 Aug;161A(8):1897-903. doi: 10.1002/ajmg.a.36023. Epub 2013 Jul 3.


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.

Keywords: FXS; MMP-9; metalloproteinases; minocycline.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • Fragile X Syndrome / drug therapy
  • Fragile X Syndrome / enzymology
  • Humans
  • Matrix Metalloproteinase 9 / blood*
  • Mice
  • Minocycline / therapeutic use*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology


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