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Open AccessArticle

Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome

1
Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA
2
Center for Neural Science, New York University, New York, NY 10003, USA
3
MIND Institute, University of California, Davis, Sacramento, CA 95817, USA
4
Department of Public Health Sciences, University of California, Davis, Davis, CA 95616, USA
5
NYU Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA
6
Center for Brain Development and Repair, Institute of Stem Cell Science and Regenerative Medicine, Bangalore 560065, India
7
Department of Pediatrics, University of California Davis, Sacramento, CA 95817, USA
*
Author to whom correspondence should be addressed.
These authors contributed to the manuscript equally.
Brain Sci. 2020, 10(6), 361; https://doi.org/10.3390/brainsci10060361
Received: 19 May 2020 / Revised: 5 June 2020 / Accepted: 8 June 2020 / Published: 10 June 2020
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. View Full-Text
Keywords: biomarker; MMP9; RAS; metformin; Fragile-X syndrome biomarker; MMP9; RAS; metformin; Fragile-X syndrome
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MDPI and ACS Style

Jasoliya, M.; Bowling, H.; Petrasic, I.C.; Durbin-Johnson, B.; Klann, E.; Bhattacharya, A.; Hagerman, R.; Tassone, F. Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome. Brain Sci. 2020, 10, 361. https://doi.org/10.3390/brainsci10060361

AMA Style

Jasoliya M, Bowling H, Petrasic IC, Durbin-Johnson B, Klann E, Bhattacharya A, Hagerman R, Tassone F. Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome. Brain Sciences. 2020; 10(6):361. https://doi.org/10.3390/brainsci10060361

Chicago/Turabian Style

Jasoliya, Mittal; Bowling, Heather; Petrasic, Ignacio C.; Durbin-Johnson, Blythe; Klann, Eric; Bhattacharya, Aditi; Hagerman, Randi; Tassone, Flora. 2020. "Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome" Brain Sci. 10, no. 6: 361. https://doi.org/10.3390/brainsci10060361

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