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Cited by 16Genetics and Neurodevelopmental DisordersAutism Spectrum Disorder ResearchDown syndrome and intellectual disability research

Combining Lovastatin and Minocycline for the Treatment of Fragile X Syndrome: Results From the LovaMiX Clinical Trial

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Champigny, Camille, Morin-Parent, Florence, Bellehumeur-Lefebvre, Laurence, Çaku, Artuela, Lepage, Jean-François, Corbin, François·2022·Frontiers in Psychiatry
DOI 10.3389/fpsyt.2021.762967PMC PMC8763805
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Abstract

Background: Limited success of previous clinical trials for Fragile X syndrome (FXS) has led researchers to consider combining different drugs to correct the pleiotropic consequences caused by the absence of the Fragile X mental retardation protein (FMRP). Here, we report the results of the LovaMiX clinical trial, the first trial for FXS combining two disease-modifying drugs, lovastatin, and minocycline, which have both shown positive effects when used independently. Aim: The main goals of the study were to assess the safety and efficacy of a treatment combining lovastatin and minocycline for patients with FXS. Design: Pilot Phase II open-label clinical trial. Patients with a molecular diagnostic of FXS were first randomized to receive, in two-step titration either lovastatin or minocycline for 8 weeks, followed by dual treatment with lovastatin 40 mg and minocycline 100 mg for 2 weeks. Clinical assessments were performed at the beginning, after 8 weeks of monotherapy, and at week 20 (12 weeks of combined therapy). Outcome Measures: The primary outcome measure was the Aberrant Behavior Checklist-Community (ABC-C) global score. Secondary outcome measures included subscales of the FXS specific ABC-C (ABC-C FX), the Anxiety, Depression, and Mood Scale (ADAMS), the Social Responsiveness Scale (SRS), the Behavior Rating Inventory of Executive Functions (BRIEF), and the Vineland Adaptive Behavior Scale second edition (VABS-II). Results: Twenty-one individuals out of 22 completed the trial. There were no serious adverse events related to the use of either drugs alone or in combination, suggesting good tolerability and safety profile of the combined therapy. Significant improvement was noted on the primary outcome measure with a 40% decrease on ABC-C global score with the combined therapy. Several outcome measures also showed significance. Conclusion: The combination of lovastatin and minocycline is safe in patients for FXS individuals and appears to improve several elements of the behavior. These results set the stage for a larger, placebo-controlled double-blind clinical trial to confirm the beneficial effects of the combined therapy.

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Authors
Champigny, C., Morin-Parent, F., Bellehumeur-Lefebvre, L., Çaku, A., Lepage, J.-F., & Corbin, F.
Affiliations
Université de Sherbrooke (CA)
Corresponding author
Corbin, François
ORCID
Venue
Frontiers in Psychiatry
Publisher
Frontiers Media SA
Published
2022-01-04
Volume
12
Pages
762967-762967
ISSN
1664-0640 (ISSN-L)
DOI
10.3389/fpsyt.2021.762967
PMC
PMC8763805
OpenAlex
W4205670823
Cited by
16
References
37
Citations by year
2026: 2 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 1
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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, lovastatin, minocycline, combination therapy, FMRP, disease-modifying therapy, aberrant behavior, social responsiveness, executive function, adaptive behavior, treatment safety

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