Abstract
Neuroinflammatory mechanisms have been implicated in the pathophysiology of autism spectrum disorder (ASD). Minocycline is a matrix metalloproteinase inhibitor 9 (MMP9) inhibitor tetracycline antibiotic with known anti-inflammatory properties. In preclinical animal models of ASD, minocycline has demonstrated potential positive effects on phenotypes that may have relevance to ASD. We conducted the first placebo-controlled study of minocycline in ASD. This double-blind, placebo-controlled crossover trial employed four week treatment periods with a two week washout period. Twenty-four 12–22 year olds (mean age 17.4 years; range 12.9–22.5 years) with ASD were enrolled. Overall minocycline was well tolerated. No minocycline-associated clinical changes were noted with treatment on any performance or clinician or caregiver completed measures were noted. We hypothesize that either minocycline does not have potential therapeutic effects in ASD or our project was underpowered to define potential subject subgroups who may potentially respond positively to this drug.
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Abbreviations
- ASD:
-
Autism spectrum disorder
- IRB:
-
Institutional review board
- DSM 5:
-
Diagnostic and statistical manual of mental disorders, fifth edition
- ABC:
-
Aberrant behavior checklist
- CFQL-2:
-
Child and family quality of life-second edition
- RBANS:
-
Repeatable battery for the assessment of neuropsychological status
- WJ-3:
-
Woodcock Johnson 3rd edition
- ADOS:
-
Autism diagnostic observation schedule
- CGI-I:
-
Clinical global impressions improvement subscale
- SB-V:
-
Stanford-Binet 5th edition
- SCQ:
-
Social communication questionnaire
- VABS:
-
Vineland adaptive behavior scale 3rd edition
- WASI:
-
Wechsler abbreviated scale of intelligence scale-second edition
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Funding
This project was funded by Autism Speaks.
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CAE, BLH, and DQB conceived of the experimental design in this project. PH is the study statistician and created the project analysis plan and conducted all post-study analyses per the analysis plan. CAE, RCS, MW, LMS, KH, EVP, NO, RVT, BLH, DQB all participated in data acquisition, subject measurement, and in data interpretation. CAE wrote the first draft manuscript. All authors participated in manuscript editing and approved of the final submission.
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Guardians of all youth participants provided written informed consent prior to study enrollment. Assent was obtained from enrolled youth when possible. For adult subjects, those with a legal guardian had guardian consent and assent from the adult participant when possible. For adult subject who are their own guardian, consent was obtained from the subject themselves.
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Erickson, C.A., Shaffer, R.C., Will, M. et al. Brief Report: A Double-Blind, Placebo-Controlled, Crossover, Proof-of-Concept Study of Minocycline in Autism Spectrum Disorder. J Autism Dev Disord (2023). https://doi.org/10.1007/s10803-023-06132-1
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DOI: https://doi.org/10.1007/s10803-023-06132-1