title: Self-adjuvanted hyaluronate--antigenic peptide conjugate for transdermal treatment of muscular dystrophy.
abstract: Duchenne's muscular dystrophy (DMD) is a neuromuscular disorder accompanied with muscle weakness and wasting. Since myostatin was reported to be a key regulator of muscle wasting, myostatin inhibitors have been investigated as therapeutic candidates for the treatment of muscular diseases. Here, we report an antigenic peptide of myostatin fragment (MstnF) conjugated to hyaluronate (HA) with a low molecular weight (MW, 17 kDa) for transdermal immunotherapy of DMD. Facilitating the transdermal delivery, the low MW HA showed a boosting effect on the immunization of MstnF possibly by engaging both toll-like receptors and cluster of differentiation 44 (CD44). In vivo two-photon microscopy clearly visualized the effective transdermal penetration of HA-MstnF conjugates into deep intact skin layers. The transdermal immunization of mdx mice significantly increased antibody titers against myostatin. Furthermore, the mdx mice immunized with HA-MstnF conjugates resulted in statistically significant improvement in the biochemical and pathological status of skeletal musculature as well as functional behaviors.
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 790-784, Republic of Korea.
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Kong
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Dong Kyung
authors.initials: DK
authors.lastname: Sung
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 790-784, Republic of Korea.
authors.forename: Hyemin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 790-784, Republic of Korea.
authors.forename: Jeong-A
authors.initials: JA
authors.lastname: Yang
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Ieronimakis
authors.affiliation: Wellman Center for Photomedicine and Harvard Medical School, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Ki Su
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, Republic of Korea.
authors.forename: Jeehun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
authors.forename: Deok-Ho
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Wellman Center for Photomedicine and Harvard Medical School, Massachusetts General Hospital, Cambridge, MA 02139, USA.
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Yun
authors.affiliation: Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 790-784, Republic of Korea. Electronic address: skhanb@postech.ac.kr.
authors.forename: Sei Kwang
authors.initials: SK
authors.lastname: Hahn
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects; D004705:Endocytosis / Q000187:drug effects; D006820:Hyaluronic Acid / Q000494:pharmacology*; D007114:Immunization; D018836:Inflammation Mediators / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D036641:Microscopy, Fluorescence, Multiphoton; D008970:Molecular Weight; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D055435:Myostatin / Q000627:therapeutic use; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D016207:Cytokines; D018836:Inflammation Mediators; D055435:Myostatin; D010455:Peptides; D006820:Hyaluronic Acid
keywords: Conjugate; Hyaluronate; Peptide; Transdermal; Vaccine