Side Effects of Minocycline Treatment in Patients With Fragile X Syndrome and Exploration of Outcome Measures

M.I.N.D. Institute, University of California at Davis Medical Center, USA.
American Journal on Intellectual and Developmental Disabilities (Impact Factor: 2.08). 09/2010; 115(5):433-43. DOI: 10.1352/1944-7558-115.5.433
Source: PubMed


Minocycline can rescue the dendritic spine and synaptic structural abnormalities in the fragile X knock-out mouse. This is a review and preliminary survey to document side effects and potential outcome measures for minocycline use in the treatment of individuals with fragile X syndrome. We surveyed 50 patients with fragile X syndrome who received minocycline for at least 2 weeks and found that the most common reported side effect is gastrointestinal difficulty, including loss of appetite. The families reported an improvement in language and behavioral areas. Outcome measures in the design of future randomized clinical trials should include both behavioral and language measures. As with any other treatments, we emphasize that randomized clinical trials are needed to determine the efficacy of minocycline in fragile X syndrome.

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Available from: Andrea Schneider
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    • "analysis of postmortem FXS brain tissue samples also indicate elevated levels of MMP - 9 protein in both the hippocampus and neocortex ( Gkogkas et al . , 2014 ; Sidhu et al . , 2014 ) . Minocycline treatment reduces plasma levels of MMP - 9 in most but not all subjects , and is associated with improvements in behavior ( Paribello et al . , 2010 ; Utari et al . , 2010 ; Dziembowska et al . , 2013 ; Leigh et al . , 2013 ) and a reversal of habituation deficits in auditory event related potentials ( Schneider et al . , 2013 ) . This suggests that MMP - 9 suppression may be a useful therapeutic approach . Together these studies indicate that increased MMP - 9 levels in FXS may underlie molecular , cellu"
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    • "High MMP-9 activity levels are also lowered by minocycline in fragile X syndrome patients (Dziembowska et al., 2013). Notably, minocycline has been tested in clinical trials to treat fragile X syndrome and shown to provide significant functional benefits (Paribello et al., 2010; Utari et al., 2010; Leigh et al., 2013). Matrix metalloproteinases have also been implicated in other forms of autism (Abdallah and Miche1, 2013). "
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    • "Following the results of studies that showed treatment with mGluR5 antagonists, including mavoglurant, could rescue several synaptic phenotypes in animal models (Choi et al. 2010; de Vrij et al. 2008; Levenga et al. 2011; McBride et al. 2005; Tucker et al. 2006; Yan et al. 2005), it was hypothesized that mavoglurant had the potential to treat the underlying pathophysiology of FXS, thus differing from current pharmacotherapy for FXS which is symptom-driven. Other agents targeting specific molecular pathways are in development for FXS (Table 3); these include RG7090 (RO4917523), another mGluR5 antagonist; STX209 (arbaclofen, R-baclofen), a γ-aminobutyric acid type B (GABA B ) receptor agonist (Berry-Kravis et al. 2012); and minocycline, a matrix metalloproteinase-9 antagonist (Bilousova et al. 2009; Leigh et al. 2013; Paribello et al. 2010; Utari et al. 2010). All of these agents aim to address the underlying pathology of FXS by targeting specific molecular pathways. "
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