The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Open-label add-on treatment trial of minocycline in fragile X syndrome.
Open accessAbstract
BACKGROUND: Fragile X syndrome (FXS) is a disorder characterized by a variety of disabilities, including cognitive deficits, attention-deficit/hyperactivity disorder, autism, and other socio-emotional problems. It is hypothesized that the absence of the fragile X mental retardation protein (FMRP) leads to higher levels of matrix metallo-proteinase-9 activity (MMP-9) in the brain. Minocycline inhibits MMP-9 activity, and alleviates behavioural and synapse abnormalities in fmr1 knockout mice, an established model for FXS. This open-label add-on pilot trial was conducted to evaluate safety and efficacy of minocycline in treating behavioural abnormalities that occur in humans with FXS. METHODS: Twenty individuals with FXS, ages 13-32, were randomly assigned to receive 100 mg or 200 mg of minocycline daily. Behavioural evaluations were made prior to treatment (baseline) and again 8 weeks after daily minocycline treatment. The primary outcome measure was the Aberrant Behaviour Checklist-Community Edition (ABC-C) Irritability Subscale, and the secondary outcome measures were the other ABC-C subscales, clinical global improvement scale (CGI), and the visual analog scale for behaviour (VAS). Side effects were assessed using an adverse events checklist, a complete blood count (CBC), hepatic and renal function tests, and antinuclear antibody screen (ANA), done at baseline and at 8 weeks. RESULTS: The ABC-C Irritability Subscale scores showed significant improvement (p < 0.001), as did the VAS (p = 0.003) and the CGI (p < 0.001). The only significant treatment-related side effects were minor diarrhea (n = 3) and seroconversion to a positive ANA (n = 2). CONCLUSIONS: Results from this study demonstrate that minocycline provides significant functional benefits to FXS patients and that it is well-tolerated. These findings are consistent with the fmr1 knockout mouse model results, suggesting that minocycline modifies underlying neural defects that account for behavioural abnormalities. A placebo-controlled trial of minocycline in FXS is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Open-Label Trial NCT00858689.
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“Reduction of MMP-9 levels with minocycline in humans with FXS (Dziembowska et al., 2013) contributes to reversal of several FXS phenotypes, including behavioral deficits and enhanced auditory electrocortical activity in adults and/or adolescents with FXS (Paribello et al., 2010; Leigh et al., 2013; Schneider et al., 2013).”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Paribello et al., 2010
In the citing paper
“an open trial in adolescent and adult males with FXS demonstrated efficacy in all of the outcome measures (127).”
From Fragile X syndrome: causes, diagnosis, mechanisms, and therapeutics (2012) · cites this paper as [127]
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Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L., et al. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.65 · Cited by 838
Self-citationDisentangling the heterogeneity of autism spectrum disorder through genetic findings
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The role of immune dysfunction in the pathophysiology of autism
Onore, C., Careaga, M., & Ashwood, P. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.08.007 · Cited by 635
The translation of translational control by FMRP: therapeutic targets for FXS
Darnell, J. C., & Klann, E. (2013) · Nature Neuroscience · doi:10.1038/nn.3379 · Cited by 491
Metadata
- Authors
- Paribello, C., Tao, L., Folino, A., Berry-Kravis, E., Tranfaglia, M., Ethell, I. M., & Ethell, D. W.
- Affiliations
- Surrey Place Centre (CA)
- Fraxa Research Foundation (US)
- University of California, Riverside (US)
- Corresponding author
- Paribello, Carlo
- Venue
- BMC Neurology
- Published
- 2010-10-11
- Volume
- 10
- Issue
- 1
- Pages
- 91-91
- ISSN
- 1471-2377 (ISSN-L)
- PMC
- PMC2958860
- OpenAlex
- W2153053291
- Cited by
- 223
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 5 · 2022: 9 · 2021: 4 · 2020: 15 · 2019: 10 · 2018: 12 · 2017: 20 · 2016: 12 · 2015: 17 · 2014: 26 · 2013: 30 · 2012: 23
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMC Neurology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- FRAXA Research Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Keywords
- fragile X syndrome, minocycline, MMP-9, FMRP, behavioural abnormalities, irritability, adjunctive therapy, drug safety, adverse events, antinuclear antibodies, Fmr1 knockout mice
- MeSH terms
- Adolescent, Adult, Enzyme Inhibitors, Female, Fragile X Syndrome, Humans, Male, Minocycline, Pilot Projects, Treatment Outcome, Young Adult
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