• ABC Irritability subtest score [ Time Frame: Baseline, then at 8 weeks, with option for 1 year extension ] [ Designated as safety issue: No ]
  

• Parent Defined Target Symptoms Scale-Visual [ Time Frame: Baseline, then at 8 weeks, with option for 1 year extension ] [ Designated as safety issue: No ]
  
• Clinical Global Impression Scale [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  
• Stanford Binet 5 (SB5) [ Time Frame: Baseline, and at 1 year ] [ Designated as safety issue: No ]
  
• The Peabody Picture Vocabulary Test Third Edition (PPVT-III) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  
• The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  
• Non-Verbal Associative Learning Task (NVALT) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  
• Vineland Adaptive Behaviour Scales (VABS) [ Time Frame: Baseline, then at 8 weeks with option for 1 year extension ] [ Designated as safety issue: No ]
  

Drug: Minocycline
50-100 mg PO BID for 8 weeks with an option for a 1 year extension.

Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment and is also associated with a range of learning disabilities, neurological problems, such as seizures, and behavioural difficulties. For many individuals with FXS, behavioural difficulties result in severe problems within the family and community, particularly in the form of agitation, temper outbursts, hyperactivity, and aggression. These problems often require a variety of psychopharmacological and behavioural approaches. Although a variety of medications can be helpful in FXS there are no targeted interventions based on molecular abnormalities that have been studied.

Defects in dendritic spine formation have been found in the brains of patients with Fragile X, suggesting these structures may represent an anatomical and physiological basis for the cognitive deficits associated with this disorder. Recent research has suggested that minocycline may have a specific benefit in the treatment of FXS.

Minocycline is an antibiotic that has been found to inhibit the activity of matrix metallo-proteinase-9 (MMP-9), which is up-regulated in the hippocampus of FMR1 KO mice and may be responsible for the immature dendritic spine profile of hippocampal neurons. Minocycline has recently been used to treat the FXS KO mouse model for Fragile X, and was found to rescue this abnormal phenotype by inducing the formation of mature dendritic spines in FMR1 KO hippocampal neurons, both in vitro and in vivo. Minocycline treated FXS KO mice also performed significantly better in the elevated maze, a cognitive performance test that measures activity and anxiety.

Exciting preclinical effects of minocycline with regard to the FXS disease model have led to this pilot proposal, which is designed to generate preliminary data that could be used to support a larger clinical trial.

The overall hypothesis is that minocycline is a specific molecular targeted treatment for FXS that will display beneficial effects on disruptive behaviour and possibly other associated features of FXS via a reduction in MMP-9 activity.