Blood‐based biomarkers predictive of metformin target engagement in fragile X syndrome

Mittal Jasoliya, Heather Bowling, Ignacio Cortina Petrasic, Blythe Durbin‐johnson, Eric Klann, Aditi Bhattacharya, Randi Hagerman, Flora Tassone

Research output: Contribution to journalArticlepeer-review


Recent advances in neurobiology have provided several molecular entrees for targeted treatments for Fragile X syndrome (FXS). However, the efficacy of these treatments has been demonstrated mainly in animal models and has not been consistently predictive of targeted drugs’ response in the preponderance of human clinical trials. Because of the heterogeneity of FXS at various levels, including the molecular level, phenotypic manifestation, and drug response, it is critically important to identify biomarkers that can help in patient stratification and prediction of therapeutic efficacy. The primary objective of this study was to assess the ability of molecular biomarkers to predict phenotypic subgroups, symptom severity, and treatment response to metformin in clinically treated patients with FXS. We specifically tested a triplex protein array comprising of hexokinase 1 (HK1), RAS (all isoforms), and Matrix Metalloproteinase 9 (MMP9) that we previously demonstrated were dysregulated in the FXS mouse model and in blood samples from patient with FXS. Seventeen participants with FXS, 12 males and 5 females, treated clinically with metformin were included in this study. The disruption in expression abundance of these proteins was normalized and associated with significant self‐reported improvement in clinical phenotypes (CGI‐I in addition to BMI) in a subset of participants with FXS. Our preliminary findings suggest that these proteins are of strong molecular relevance to the FXS pathology that could make them useful molecular biomarkers for this syndrome.

Original languageEnglish (US)
Article number361
Pages (from-to)1-12
Number of pages12
JournalBrain Sciences
Issue number6
StatePublished - Jun 2020


  • Biomarker
  • Fragile‐X syndrome
  • MMP9
  • Metformin
  • RAS

ASJC Scopus subject areas

  • General Neuroscience


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