دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Blood-Based Biomarkers Predictive of Metformin Target Engagement in Fragile X Syndrome.
المؤلفون: Jasoliya M; Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA., Bowling H; Center for Neural Science, New York University, New York, NY 10003, USA., Petrasic IC; MIND Institute, University of California, Davis, Sacramento, CA 95817, USA., Durbin-Johnson B; Department of Public Health Sciences, University of California, Davis, Davis, CA 95616, USA., Klann E; Center for Neural Science, New York University, New York, NY 10003, USA.; NYU Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA., Bhattacharya A; Center for Brain Development and Repair, Institute of Stem Cell Science and Regenerative Medicine, Bangalore 560065, India., Hagerman R; MIND Institute, University of California, Davis, Sacramento, CA 95817, USA.; Department of Pediatrics, University of California Davis, Sacramento, CA 95817, USA., Tassone F; Department of Biochemistry and Molecular Medicine, University of California, Davis, Sacramento, CA 95817, USA.; MIND Institute, University of California, Davis, Sacramento, CA 95817, USA.
المصدر: Brain sciences [Brain Sci] 2020 Jun 10; Vol. 10 (6). Date of Electronic Publication: 2020 Jun 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101598646 Publication Model: Electronic Cited Medium: Print ISSN: 2076-3425 (Print) Linking ISSN: 20763425 NLM ISO Abbreviation: Brain Sci Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مستخلص: 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.
References: J Dev Behav Pediatr. 2013 Apr;34(3):147-55. (PMID: 23572165)
J Dev Behav Pediatr. 2007 Apr;28(2):133-8. (PMID: 17435464)
Autism. 2001 Dec;5(4):407-29. (PMID: 11777257)
J Neurosci. 2014 Jul 23;34(30):9867-79. (PMID: 25057190)
Cell Rep. 2014 Dec 11;9(5):1742-1755. (PMID: 25466251)
Brain Res. 2012 Feb 23;1439:7-14. (PMID: 22265702)
Front Cell Neurosci. 2015 Jul 29;9:280. (PMID: 26283917)
Wiley Interdiscip Rev Cogn Sci. 2014 Jul;5(4):501-508. (PMID: 25485036)
Am J Med Genet A. 2013 Aug;161A(8):1897-903. (PMID: 23824974)
J Autism Dev Disord. 1998 Dec;28(6):499-508. (PMID: 9932236)
Nat Rev Dis Primers. 2017 Sep 29;3:17065. (PMID: 28960184)
Pediatrics. 1995 May;95(5):744-52. (PMID: 7724315)
Brain Sci. 2019 Mar 11;9(3):. (PMID: 30862080)
BMC Neurol. 2010 Oct 11;10:91. (PMID: 20937127)
Am J Hum Genet. 2000 Jan;66(1):6-15. (PMID: 10631132)
J Mol Diagn. 2008 Jan;10(1):43-9. (PMID: 18165273)
Clin Genet. 2018 Feb;93(2):216-222. (PMID: 28436599)
Neuroscience. 2013 Aug 29;246:186-98. (PMID: 23660195)
Curr Genomics. 2011 May;12(3):216-24. (PMID: 22043169)
Nat Med. 2017 Jun;23(6):674-677. (PMID: 28504725)
J Neuroimmunol. 2000 Sep 22;109(2):221-7. (PMID: 10996224)
J Med Genet. 2008 Aug;45(8):498-9. (PMID: 18413371)
Mol Psychiatry. 2017 Aug;22(8):1140-1148. (PMID: 27090306)
J Autism Dev Disord. 2007 Apr;37(4):738-47. (PMID: 17031449)
Curr Opin Pharmacol. 2015 Feb;20:124-34. (PMID: 25488569)
Am J Med Genet. 1999 May 28;84(3):250-61. (PMID: 10331602)
J Med Genet. 2009 Feb;46(2):94-102. (PMID: 18835858)
Am J Ment Retard. 2008 Nov;113(6):427-38. (PMID: 19127654)
Brain Dev. 2017 Jun;39(6):483-492. (PMID: 28242040)
Psychiatry (Edgmont). 2007 Jul;4(7):28-37. (PMID: 20526405)
Am J Intellect Dev Disabil. 2010 Sep;115(5):433-43. (PMID: 20687826)
Mol Autism. 2020 May 27;11(1):41. (PMID: 32460900)
Am J Hum Genet. 2009 Oct;85(4):503-14. (PMID: 19804849)
Nat Commun. 2019 Apr 12;10(1):1710. (PMID: 30979884)
Clin Chem. 2010 Mar;56(3):399-408. (PMID: 20056738)
Neuron. 2014 Jan 22;81(2):333-48. (PMID: 24462097)
معلومات مُعتمدة: U54 HD082013 United States HD NICHD NIH HHS; UL1 TR001860 United States TR NCATS NIH HHS; SPO 18-4412 Azrieli Foundation; U54 HD079125 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Fragile-X syndrome; MMP9; RAS; biomarker; metformin
تواريخ الأحداث: Date Created: 20200614 Latest Revision: 20210720
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7349631
DOI: 10.3390/brainsci10060361
PMID: 32531912
قاعدة البيانات: MEDLINE
الوصف
تدمد:2076-3425
DOI:10.3390/brainsci10060361