title: An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome.
abstract: BACKGROUND
  Minocycline, a member of the tetracycline family, has a low risk of adverse effects and an ability to improve behavioral performance in humans with cognitive disruption. We performed a single-arm open-label trial in which 25 children diagnosed with Angelman syndrome (AS) were administered minocycline to assess the safety and tolerability of minocycline in this patient population and determine the drug's effect on the cognitive and behavioral manifestations of the disorder.
  
  
  METHODS
  Participants, age 4-12 years old, were randomly selected from a pool of previously screened children for participation in this study. Each child received 3 milligrams of minocycline per kilogram of body weight per day for 8 weeks. Participants were assessed during 3 study visits: baseline, after 8-weeks of minocycline treatment and after an 8-week wash out period. The primary outcome measure was the Bayley Scales of Infant and Toddler Development 3rd Edition (BSID-III). Secondary outcome measures included the Clinical Global Impressions Scale (CGI), Vineland Adaptive Behavior Scales 2nd Edition (VABS-II), Preschool Language Scale 4th Edition (PLS-IV) and EEG scores. Observations were considered statistically significant if p < 0.05 using ANOVA and partial eta squared (η(2)) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett's post hoc testing.
  
  
  RESULTS
  Significant improvement in the mean raw scores of the BSID-III subdomains communication and fine motor ability as well as the subdomains auditory comprehension and total language ability of the PLS-IV when baseline scores were compared to scores after the washout period. Further, improvements were observed in the receptive communication subdomain of the VABS-II after treatment with minocycline. Finally, mean scores of the BSID-III self-direction subdomain and CGI scale score were significantly improved both after minocycline treatment and after the wash out period.
  
  
  CONCLUSIONS
  The clinical and neuropsychological measures suggest minocycline was well tolerated and causes improvements in the adaptive behaviors of this sample of children with Angelman syndrome. While the optimal dosage and the effects of long-term use still need to be determined, these findings suggest further investigation into the effect minocycline has on patients with Angelman syndrome is warranted.
  
  
  BACKGROUND
  NCT01531582 - clinicaltrials.gov.
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. jgrieco1@health.usf.edu.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Grieco
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. sblanken@health.usf.edu.
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Ciarlone
authors.affiliation: Department of Pediatrics, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. mgieron@health.usf.edu.|Department of Neurology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. mgieron@health.usf.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Gieron-Korthals
authors.affiliation: Departments of Psychiatry and Behavioral Neurosciences, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. mschoenb@health.usf.edu.|Department of Neurology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. mschoenb@health.usf.edu.|University of South Florida Health's Byrd Alzheimer's Research Institute, 4001 E Fletcher Avenue, Tampa, FL, 33613, USA. mschoenb@health.usf.edu.
authors.forename: Mike R
authors.initials: MR
authors.lastname: Schoenberg
authors.affiliation: University of South Florida Health's Byrd Alzheimer's Research Institute, 4001 E Fletcher Avenue, Tampa, FL, 33613, USA. asmith2@health.usf.edu.
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Smith
authors.affiliation: Departments of Psychiatry and Behavioral Neurosciences, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. rphilpot@health.usf.edu.
authors.forename: Rex M
authors.initials: RM
authors.lastname: Philpot
authors.affiliation: Mater Research Institute, University of Queensland, St Lucia, QLD, 4072, Australia. honey.heussler@mater.org.au.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Heussler
authors.affiliation: University of South Florida Health's Byrd Alzheimer's Research Institute, 4001 E Fletcher Avenue, Tampa, FL, 33613, USA. jbanko@health.usf.edu.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Banko
authors.affiliation: Department of Molecular Pharmacology and Physiology, University of South Florida, Morsani College of Medicine, 12901 Bruce B Downs Boulevard, Tampa, FL, 33612, USA. eweeber@health.usf.edu.|University of South Florida Health's Byrd Alzheimer's Research Institute, 4001 E Fletcher Avenue, Tampa, FL, 33613, USA. eweeber@health.usf.edu.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
mesh_terms: D017204:Angelman Syndrome / Q000150:complications / Q000188:drug therapy*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D006801:Humans; D008297:Male; D008911:Minocycline / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D008911:Minocycline