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Randomized Controlled Trial
. 2024 Sep;17(9):1944-1956.
doi: 10.1002/aur.3222. Epub 2024 Sep 9.

Neurophysiological effects of a combined treatment of lovastatin and minocycline in patients with fragile X syndrome: Ancillary results of the LOVAMIX randomized clinical trial

Florence Morin-Parent  1   2 , Camille Champigny  2   3 , Samantha Côté  1 , Teddy Mohamad  1   2 , Seyede Anis Hasani  1   2 , Artuela Çaku  2   3 , François Corbin  2   3 , Jean-François Lepage  1   2
Affiliations
Randomized Controlled Trial

Neurophysiological effects of a combined treatment of lovastatin and minocycline in patients with fragile X syndrome: Ancillary results of the LOVAMIX randomized clinical trial

Florence Morin-Parent et al. Autism Res. 2024 Sep.

Abstract

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease-modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting-motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short-intracortical inhibition, a marker of GABAa-mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379).

Keywords: dual therapy; fragile X syndrome; lovastatin; minocycline; transcranial magnetic stimulation.

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References

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