High MMP-9 activity levels in fragile X syndrome are lowered by minocycline Academic Article uri icon

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

  • Dziembowska, Magdalena
  • Pretto, Dalyir I
  • Janusz, Aleksandra
  • Kaczmarek, Leszek
  • Leigh, Mary Jacena
  • Gabriel, Nielsen
  • Durbin-Johnson, Blythe
  • Hagerman, Randi J
  • Tassone, Flora

publication date

  • 2013