Research Summary: National Fragile X Foundation – Translational Research Grant
Randi Hagerman MD – $100,000
UC Davis MIND Institute
This project will study the efficacy of the antibiotic drug minocycline for children ages 4 to 16 years who have Fragile X syndrome (FXS). Dr. Hagerman believes the study will provide sufficient data to submit a large multi-center controlled trial of minocycline that could involve many of the centers associated with the Fragile X Clinical & Research Consortium.
Advances in understanding the molecular biology of FXS have led to new targeted treatments that have the potential to reverse the central nervous system abnormalities in the condition. To date, the focus of targeted treatments has been on the use of mGluR5 antagonists in animal models and in humans with FXS. However, these medications are not readily available other than through a research protocol approved by the Food and Drug Administration in conjunction with the pharmacological company that has developed the mGluR5 antagonist.
Recent studies have shown improvements in synaptic maturation, behavior and cognition after a one-month minocycline treatment in the newborn knock out Fragile X mouse (Bilousova et al., 2009). The Bilousova study demonstrated that minocycline lowered matrix metalloproteinase 9 (MMP9) levels in the KO mouse which are elevated in the absence of FMRP. Our preliminary survey of more than 50 individuals with FXS treated with minocycline for an average of three months has demonstrated improvements in language, attention and behavior in some individuals, with primarily mild side effects.