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Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor‐β2
Author(s) -
Logan Ann,
Green Jonathan,
Hunter Allison,
Jackson Ronald,
Berry Martin
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00654.x
Subject(s) - extracellular matrix , fibrosis , wound healing , monoclonal antibody , biology , transforming growth factor beta , immunology , transforming growth factor , pathology , fibronectin , microbiology and biotechnology , cancer research , medicine , antibody
The transforming growth factor‐βs (TGF‐βs) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF‐β2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti‐TGF‐β2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial‐limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound‐responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti‐fibrotic TGF‐β antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.