PMID- 23566357
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140520
LR  - 20211021
IS  - 1866-1947 (Print)
IS  - 1866-1955 (Electronic)
IS  - 1866-1947 (Linking)
VI  - 5
IP  - 1
DP  - 2013
TI  - A pilot open-label trial of minocycline in patients with autism and regressive 
      features.
PG  - 9
LID - 10.1186/1866-1955-5-9 [doi]
AB  - BACKGROUND: Minocycline is a tetracycline derivative that readily crosses the 
      blood brain barrier and appears to have beneficial effects on neuroinflammation, 
      microglial activation and neuroprotection in a variety of neurological disorders. 
      Both microglial activation and neuroinflammation have been reported to be 
      associated with autism. The study was designed to evaluate the effects of 
      minocycline treatment on markers of neuroinflammation and autism symptomatology 
      in children with autism and a history of developmental regression. METHODS: 
      Eleven children were enrolled in an open-label trial of six months of minocycline 
      (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected 
      and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the 
      end of minocycline treatment and were analyzed for markers of neuroinflammation. 
      RESULTS: Clinical improvements were negligible. The laboratory assays 
      demonstrated significant changes in the expression profile of the truncated form 
      of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor 
      (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 
      macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature 
      BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine 
      CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no 
      significant changes were observed in CSF or serum in chemokines such as CCL2 
      (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1beta when pre- and 
      post-treatment levels of these proteins were compared. No significant pre- and 
      post-treatment changes were seen in the profiles of plasma metalloproteinases, 
      putative targets of the effects of minocycline. CONCLUSIONS: Changes in the pre- 
      and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) 
      in serum, suggest that minocycline may have effects in the CNS by modulating the 
      production of neurotrophic growth factors. However, in this small group of 
      children, no clinical improvements were observed during or after the six months 
      of minocycline administration. TRIAL REGISTRATION: NCT00409747.
FAU - Pardo, Carlos A
AU  - Pardo CA
AD  - Department of Neurology, Pathology 627, Johns Hopkins University School of 
      Medicine, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
FAU - Buckley, Ashura
AU  - Buckley A
AD  - Pediatrics & Developmental Neuroscience Branch, National Institute of Mental 
      Health, 10 Center Drive, Bldg 10/RM 1C250/MSC 1255, Bethesda, MD, 20892, USA.
FAU - Thurm, Audrey
AU  - Thurm A
AD  - Pediatrics & Developmental Neuroscience Branch, National Institute of Mental 
      Health, 10 Center Drive, Bldg 10/RM 1C250/MSC 1255, Bethesda, MD, 20892, USA.
FAU - Lee, Li-Ching
AU  - Lee LC
AD  - Department of Epidemiology, Johns Hopkins University Bloomberg School of Public 
      Health, 615 N. Wolfe Street, Room E6032, Baltimore, MD, 21205, USA.
FAU - Azhagiri, Arun
AU  - Azhagiri A
AD  - Department of Neurology, Pathology 627, Johns Hopkins University School of 
      Medicine, 600 North Wolfe Street, Baltimore, MD, 21287, USA.
FAU - Neville, David M
AU  - Neville DM
AD  - Pediatrics & Developmental Neuroscience Branch, National Institute of Mental 
      Health, 10 Center Drive, Bldg 10/RM 1C250/MSC 1255, Bethesda, MD, 20892, USA.
FAU - Swedo, Susan E
AU  - Swedo SE
AD  - Pediatrics & Developmental Neuroscience Branch, National Institute of Mental 
      Health, 10 Center Drive, Bldg 10/RM 1C250/MSC 1255, Bethesda, MD, 20892, USA.
LA  - eng
SI  - ClinicalTrials.gov/NCT00409747
PT  - Journal Article
DEP - 20130408
PL  - England
TA  - J Neurodev Disord
JT  - Journal of neurodevelopmental disorders
JID - 101483832
PMC - PMC3663771
OTO - NOTNLM
OT  - Autism
OT  - BDNF
OT  - Chemokines
OT  - Clinical trial
OT  - Cytokines
OT  - Metalloproteinases
OT  - Microglia
OT  - Minocycline
OT  - Neuroinflammation
OT  - Neurotrophins
EDAT- 2013/04/10 06:00
MHDA- 2013/04/10 06:01
PMCR- 2013/01/01
CRDT- 2013/04/10 06:00
PHST- 2012/11/27 00:00 [received]
PHST- 2013/03/20 00:00 [accepted]
PHST- 2013/04/10 06:00 [entrez]
PHST- 2013/04/10 06:00 [pubmed]
PHST- 2013/04/10 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 1866-1955-5-9 [pii]
AID - 10.1186/1866-1955-5-9 [doi]
PST - ppublish
SO  - J Neurodev Disord. 2013;5(1):9. doi: 10.1186/1866-1955-5-9. Epub 2013 Apr 8.