Lovastatin corrects ERK pathway hyperactivation in fragile X syndrome: potential of platelet’s signaling cascades as new outcome measures in clinical trials

Abstract

Aim: To establish whether platelets from fragile X syndrome (FXS) individuals recapitulate FXS mouse neurons’ defects in ERK and Akt pathways, and to evaluate the effect of lovastatin on these pathways.

Methods: ERK and Akt phosphorylation (pERK, pAkt) statuses were assessed with quantitative Western blotting before and after a 12-week lovastatin trial.

Results: Levels of pERK and pAkt were increased in FXS platelets, and lovastatin specifically normalized ERK activity. Changes in ERK phosphorylation were correlated with clinical response to lovastatin.

Conclusions: Platelets’ signaling pathways provide biomarkers that can be used as treatment outcome measures in FXS clinical trials.

Keywords:

• Akt
• biomarkers
• blood platelets
• genetic diseases
• study model

Acknowledgements

We warmly thank all fragile X individuals and their family for having participated in the lovastatin trial and in this study. We are grateful to Prof. Robert Day, Sylvie Auger, Nathalie Guay, Marjolaine Champagne, Andréanne Fabi and Simon Pellerin for technical assistance, and to Sophie Gagnon for neuropsychological assessments.

Disclosure statement

The authors declare no competing financial interest.

Funding information

Université de Sherbrooke, CHUS Research Center, and FRAXA Research Foundation.

D.P. holds a Frederick Banting and Charles Best Canada Graduate Scholarship Master Award from the Canadian Institutes of Health Research (CIHR) and an MD-MSc Graduate Scholarship Master Award from the Fonds de Recherche du Québec – Santé (FRQS).