A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma: Implications in DMD Diagnosis and Clinical Monitoring

Rossi, RacheleUCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.;Univ Ferrara, Dept Med Sci, Med Genet Unit, I-44121 Ferrara, Italy. (författare)

A Proof of Principle Proteomic Study Detects Dystrophin in Human Plasma : Implications in DMD Diagnosis and Clinical Monitoring

QC 20230425
Duchenne muscular dystrophy (DMD) is a rare neuromuscular disease caused by pathogenic variations in the DMD gene. There is a need for robust DMD biomarkers for diagnostic screening and to aid therapy monitoring. Creatine kinase, to date, is the only routinely used blood biomarker for DMD, although it lacks specificity and does not correlate with disease severity. To fill this critical gap, we present here novel data about dystrophin protein fragments detected in human plasma by a suspension bead immunoassay using two validated anti-dystrophin-specific antibodies. Using both antibodies, a reduction of the dystrophin signal is detected in a small cohort of plasma samples from DMD patients when compared to healthy controls, female carriers, and other neuromuscular diseases. We also demonstrate the detection of dystrophin protein by an antibody-independent method using targeted liquid chromatography mass spectrometry. This last assay detects three different dystrophin peptides in all healthy individuals analysed and supports our finding that dystrophin protein is detectable in plasma. The results of our proof-of-concept study encourage further studies in larger sample cohorts to investigate the value of dystrophin protein as a low invasive blood biomarker for diagnostic screening and clinical monitoring of DMD.

Johansson, CamillaKTH,Systembiologi(Swepub:kth)u1jemko2 (författare)
Heywood, WendyUCL Inst Child Hlth, Genet & Genom Med Dept, Translat Mass Spectrometry Res Grp, London W N 1EH, England. (författare)
Vinette, HeloiseUCL Inst Child Hlth, Genet & Genom Med Dept, Translat Mass Spectrometry Res Grp, London W N 1EH, England. (författare)
Jensen, GabriellaKTH,Proteinvetenskap(Swepub:kth)u1056u6d (författare)
Tegel, HannaKTH,Proteinvetenskap(Swepub:kth)u1nou8yx (författare)
Jimenez-Requena, AlbertKTH,Proteinvetenskap(Swepub:kth)u1ti38o6 (författare)
Torelli, SilviaUCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England. (författare)
Al-Khalili Szigyarto, CristinaKTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1c02mh9 (författare)
Ferlini, AlessandraUCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.;Univ Ferrara, Dept Med Sci, Med Genet Unit, I-44121 Ferrara, Italy. (författare)
UCL Great Ormond St Inst Child Hlth, Dubowitz Neuromuscular Ctr, London WC1N 1EH, England.;Univ Ferrara, Dept Med Sci, Med Genet Unit, I-44121 Ferrara, Italy.Systembiologi (creator_code:org_t)

Ingår i:International Journal of Molecular Sciences: MDPI AG24:61661-65961422-0067

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