title: Non-Invasive Biomarkers for Duchenne Muscular Dystrophy and Carrier Detection.
abstract: Non-invasive biological indicators of the absence/presence or progress of the disease that could be used to support diagnosis and to evaluate the effectiveness of treatment are of utmost importance in Duchenne Muscular Dystrophy (DMD). This neuromuscular disorder affects male children, causing weakness and disability, whereas female relatives are at risk of being carriers of the disease. A biomarker with both high sensitivity and specificity for accurate prediction is preferred. Until now creatine kinase (CK) levels have been used for DMD diagnosis but these fail to assess disease progression. Herein we examined the potential applicability of serum levels of matrix metalloproteinase 9 and matrix metalloproteinase 2, tissue inhibitor of metalloproteinases 1, myostatin (GDF-8) and follistatin (FSTN) as non-invasive biomarkers to distinguish between DMD steroid naïve patients and healthy controls of similar age and also for carrier detection. Our data suggest that serum levels of MMP-9, GDF-8 and FSTN are useful to discriminate DMD from controls (p < 0.05), to correlate with some neuromuscular assessments for DMD, and also to differentiate between Becker muscular dystrophy (BMD) and Limb-girdle muscular dystrophy (LGMD) patients. In DMD individuals under steroid treatment, GDF-8 levels increased as FSTN levels decreased, resembling the proportions of these proteins in healthy controls and also the baseline ratio of patients without steroids. GDF-8 and FSTN serum levels were also useful for carrier detection (p < 0.05). Longitudinal studies with larger cohorts are necessary to confirm that these molecules correlate with disease progression. The biomarkers presented herein could potentially outperform CK levels for carrier detection and also harbor potential for monitoring disease progression.
authors.affiliation: Research Center in Technology and Design Assistance of Jalisco State (CIATEJ, AC), National Council of Science and Technology (CONACYT), Guadalajara 44270, Mexico. monica207383614@gmail.com.
authors.forename: Monica Alejandra
authors.initials: MA
authors.lastname: Anaya-Segura
authors.affiliation: National Medical Centre \"20 de Noviembre\", Institute for Social Security of State Workers, Mexico City 03100, Mexico. elfroy77_@hotmail.com.
authors.forename: Froylan Arturo
authors.initials: FA
authors.lastname: García-Martínez
authors.affiliation: National Medical Centre \"20 de Noviembre\", Institute for Social Security of State Workers, Mexico City 03100, Mexico. wicho_unam@hotmail.com.
authors.forename: Luis Angel
authors.initials: LA
authors.lastname: Montes-Almanza
authors.affiliation: National Institute of Rehabilitation, Mexico City 14389, Mexico. bgodiaz@gmail.com.
authors.forename: Benjamín-Gomez
authors.initials: BG
authors.lastname: Díaz
authors.affiliation: Faculty of Medicine, National Autonomous University of Mexico, Mexico City 04510, Mexico. guilleavila2000@yahoo.com.
authors.forename: Guillermina
authors.initials: G
authors.lastname: Avila-Ramírez
authors.affiliation: Research Center in Technology and Design Assistance of Jalisco State (CIATEJ, AC), National Council of Science and Technology (CONACYT), Guadalajara 44270, Mexico. ialvarez@ciatej.mx.
authors.forename: Ikuri
authors.initials: I
authors.lastname: Alvarez-Maya
authors.affiliation: Studies Section of Postgraduate and Research, School of Medicine, National Polytechnic Institute, Mexico City 11340, Mexico. rmcoralv@gmail.com.
authors.forename: Ramón Mauricio
authors.initials: RM
authors.lastname: Coral-Vazquez
authors.affiliation: National Medical Centre \"20 de Noviembre\", Institute for Social Security of State Workers, Mexico City 03100, Mexico. p.mondragonteran@gmail.com.
authors.forename: Paul
authors.initials: P
authors.lastname: Mondragón-Terán
authors.affiliation: National Institute of Rehabilitation, Mexico City 14389, Mexico. rescobarmex@gmail.com.
authors.forename: Rosa Elena
authors.initials: RE
authors.lastname: Escobar-Cedillo
authors.affiliation: Asociación de Distrofia Muscular de Occidente A.C., Guadalajara 44380, Mexico. dranoemigarcia@gmail.com.|Mexican Institute of Social Security-CMNO, Guadalajara 44340, Mexico. dranoemigarcia@gmail.com.
authors.forename: Noemí
authors.initials: N
authors.lastname: García-Calderón
authors.affiliation: Faculty of Medicine, Autonomous University of Guadalajara, Guadalajara 45129, Mexico. avc200180@yahoo.com.mx.
authors.forename: Norma Alejandra
authors.initials: NA
authors.lastname: Vazquez-Cardenas
authors.affiliation: National Medical Centre \"20 de Noviembre\", Institute for Social Security of State Workers, Mexico City 03100, Mexico. rolasil@yahoo.com.mx.
authors.forename: Silvia
authors.initials: S
authors.lastname: García
authors.affiliation: National Medical Centre \"20 de Noviembre\", Institute for Social Security of State Workers, Mexico City 03100, Mexico. lblhmedgen@gmail.com.
authors.forename: Luz Berenice
authors.initials: LB
authors.lastname: López-Hernandez
mesh_terms: D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016326:Extracellular Matrix Proteins / Q000097:blood / Q000378:metabolism; D005260:Female; D006579:Heterozygote; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins
keywords: Duchenne; FSTN; GDF-8; MMP-2; MMP-9; TIMP-1; biomarkers; monitoring