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

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

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86 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1897-1903
Number of pages7
JournalAmerican Journal of Medical Genetics, Part A
Volume161
Issue number8
DOIs
StatePublished - Aug 2013

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Keywords

  • FXS
  • Metalloproteinases
  • Minocycline
  • MMP-9

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Dziembowska, M., Pretto, D. I., Janusz, A., Kaczmarek, L., Leigh, M. J., Gabriel, N., Durbin-Johnson, B., Hagerman, R. J., & Tassone, F. (2013). High MMP-9 activity levels in fragile X syndrome are lowered by minocycline. American Journal of Medical Genetics, Part A, 161(8), 1897-1903. https://doi.org/10.1002/ajmg.a.36023