title: Monoclonal antibodies for clinical trials of Duchenne muscular dystrophy therapy.
abstract: Most pathogenic mutations in Duchenne and Becker muscular dystrophies involve deletion of single or multiple exons from the dystrophin gene, so exon-specific monoclonal antibodies (mAbs) can be used to distinguish normal and mutant dystrophin proteins. In Duchenne therapy trials, mAbs can be used to identify or rule out dystrophin-positive "revertant" fibres, which have an internally-deleted dystrophin protein and which occur naturally in some Duchenne patients. Using phage-displayed peptide libraries, we now describe the new mapping of the binding sites of five dystrophin mAbs to a few amino-acids within single exons. The phage display method also confirmed previous mapping of MANEX1A (exon 1) and MANDRA1 (exon 77) by other methods. Of the 79 dystrophin exons, mAbs are now available against single exons 1, 6, 8, 12, 13, 14, 17, 21, 26, 28, 38, 41, 43, 44, 45, 46, 47, 50, 51, 58, 59, 62, 63, 75 and 77. Many have been used in clinical trials, as well as for diagnosis and studies of dystrophin isoforms.
authors.affiliation: Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UK.
authors.forename: Thanh Lam
authors.initials: TL
authors.lastname: Le
authors.affiliation: Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UK.
authors.forename: Thi Man
authors.initials: TM
authors.lastname: Nguyen
authors.affiliation: Wolfson Centre for Inherited Neuromuscular Disease, RJAH Orthopaedic Hospital, Oswestry SY10 7AG, UK; Institute for Science and Technology in Medicine, Keele University, Keele, UK. Electronic address: glenn.morris@rjah.nhs.uk.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Morris
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology*; D016189:Dystrophin / Q000737:chemistry / Q000276:immunology*; D018604:Epitope Mapping; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000276:immunology / Q000628:therapy; D020539:Sequence Analysis, Protein
chemical_list: D000911:Antibodies, Monoclonal; C484258:DMD protein, human; D016189:Dystrophin
keywords: Clinical trial; Duchenne muscular dystrophy; Dystrophin; Epitope mapping; Exon-skipping; Monoclonal antibody; Phage display; Therapy