Universität zu Köln

Walpurgis, Katja, Thomas, Andreas ORCID: 0000-0003-1199-0743, Dellanna, Frank, Schaenzer, Wilhelm and Thevis, Mario (2018). Detection of the Human Anti-ActRII Antibody Bimagrumab in Serum by Means of Affinity Purification, Tryptic Digestion, and LC-HRMS. Proteom. Clin. Appl., 12 (3). WEINHEIM: WILEY-V C H VERLAG GMBH. ISSN 1862-8354

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Abstract

PurposeInhibitors of the ActRII signaling pathways represent promising therapeutics for the treatment of muscular diseases, but also pose risks as performance-enhancing agents in sports. Bimagrumab is a human anti-ActRII antibody which was found to increase muscle mass and function by blocking ActRII signaling. As it has considerable potential for being misused as doping agent in sports, the aim of this study was to develop a mass spectrometric detection assay for doping control serum samples. Experimental designWithin this study, a detection method for Bimagrumab in human serum was developed, which combines ammonium sulfate precipitation and affinity purification with proteolytic digestion and LC-HRMS. To facilitate the unambiguous identification of the diagnostic peptides, an orthogonal IM separation was additionally performed. ResultsThe assay was successfully validated and the analysis of clinical samples demonstrated its fitness for purpose for an application in routine doping control analysis. Conclusions and clinical relevanceAlthough no myostatin inhibitors have obtained clinical approval yet, the proactive development of detection methods for emerging doping agents represents a key aspect of preventive doping research. The presented approach will expand the range of available tests for novel protein therapeutics and can readily be modified to include further target analytes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Walpurgis, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Thomas, Andreas UNSPECIFIED orcid.org/0000-0003-1199-0743 UNSPECIFIED Dellanna, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaenzer, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED Thevis, Mario UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-187702
DOI:	10.1002/prca.201700120
Journal or Publication Title:	Proteom. Clin. Appl.
Volume:	12
Number:	3
Date:	2018
Publisher:	WILEY-V C H VERLAG GMBH
Place of Publication:	WEINHEIM
ISSN:	1862-8354
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MUSCLE MASS; MYOBLAST DIFFERENTIATION; THERAPEUTIC ANTIBODIES; MYOSTATIN INHIBITORS; MUSCULAR-DYSTROPHY; CANCER CACHEXIA; SPECTROMETRY; BLOCKADE; PROTECTS; MYO-029 Multiple languages Biochemical Research Methods; Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18770