An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome

Grieco, Joseph C., Ciarlone, Stephanie L., Gieron-Korthals, Maria, Schoenberg, Mike R., Smith, Amanda G., Philpot, Rex M., Heussler, Helen S., Banko, Jessica L. and Weeber, Edwin J. (2014) An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome. BMC Neurology, 14 232: 1-9. doi:10.1186/s12883-014-0232-x

Author Grieco, Joseph C.
Ciarlone, Stephanie L.
Gieron-Korthals, Maria
Schoenberg, Mike R.
Smith, Amanda G.
Philpot, Rex M.
Heussler, Helen S.
Banko, Jessica L.
Weeber, Edwin J.
Title An open-label pilot trial of minocycline in children as a treatment for Angelman syndrome
Journal name BMC Neurology   Check publisher's open access policy
ISSN 1471-2377
Publication date 2014-12-10
Year available 2014
Sub-type Article (original research)
DOI 10.1186/s12883-014-0232-x
Open Access Status DOI
Volume 14
Issue 232
Start page 1
End page 9
Total pages 9
Place of publication London United Kingdom
Publisher BioMed Central
Collection year 2015
Language eng
Formatted abstract

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.


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 (η2) was calculated to show effect size. Multiple comparisons testing between time points were carried out using Dunnett’s post hoc testing.


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.


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.
Keyword Angelman syndrome
Cognitive impairment
Synaptic plasticity
Mouse model
Mental retardation
Therapeutic trial
In vivo
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2015 Collection
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Citation counts: TR Web of Science Citation Count  Cited 3 times in Thomson Reuters Web of Science Article | Citations
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