Add-on Pilot Trial of Minocycline to Treat Fragile X Syndrome
Condition: Fragile X Syndrome
MeSH terms: Fragile X Syndrome; Syndrome
Study type: Interventional

Summary: 
      Fragile X Syndrome (FXS) is the most common known inherited form of mental impairment,
      developmental disability and autism. Minocycline is an antibiotic that has recently been used
      to treat the mouse model for Fragile X, and was found to reverse the structural abnormalities
      that are seen their brain cells. The purpose of this research study is to determine if
      minocycline is an effective treatment for patients with fragile X syndrome (FXS).
    

Detailed description: 
      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, behavioral
      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 (Fragile X
      Mental Retardation-1 Knockout) 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.
    

Intervention name(s): Minocycline
Intervention type(s): Drug
Intervention description(s): 50-100 mg PO BID for 8 weeks with an option for a 1 year extension.
Other intervention name(s): Solodyn, Dynacin, Arestin, Minocin
Intervention MeSH terms: Minocycline
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Clinical Drug Trial