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  • Hirani, NikhilUniversity of Edinburgh (author)

Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2020-11-19
  • European Respiratory Society (ERS),2021

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:7fc87542-6130-4509-8562-2b2c126fa059
  • https://lup.lub.lu.se/record/7fc87542-6130-4509-8562-2b2c126fa059URI
  • https://doi.org/10.1183/13993003.02559-2020DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139: placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (Cmax) values ranging from 0.6 to 3 h and a plasma half-life (T1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • MacKinnon, Alison C.University of Edinburgh,Galecto Biotech ApS, Denmark (author)
  • Nicol, LisaUniversity of Edinburgh (author)
  • Ford, PaulGalecto Biotech ApS, Denmark (author)
  • Schambye, HansGalecto Biotech ApS, Denmark (author)
  • Pedersen, AndersGalecto Biotech ApS, Denmark (author)
  • Nilsson, Ulf J.Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)ok2-uni (author)
  • Leffler, HakonLund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine(Swepub:lu)mmb-hle (author)
  • Sethi, TariqGalecto Biotech ApS, Denmark (author)
  • Tantawi, SusanGalecto Biotech ApS, Denmark (author)
  • Gravelle, LiseGalecto Biotech ApS, Denmark (author)
  • Slack, Robert J.Galecto Biotech ApS, Denmark (author)
  • Mills, RossUniversity of Edinburgh (author)
  • Karmakar, UtsaUniversity of Edinburgh (author)
  • Humphries, DuncanUniversity of Edinburgh (author)
  • Zetterberg, FredrikGalecto Biotech ApS, Denmark (author)
  • Keeling, LucyExploristics Ltd (author)
  • Paul, LynImperial College London,Royal Brompton and Harefield NHS Foundation Trust (author)
  • Molyneaux, Philip L.Imperial College London,Royal Brompton and Harefield NHS Foundation Trust (author)
  • Li, FengUniversity of Edinburgh (author)
  • Funston, WendyUniversity of Newcastle upon Tyne (author)
  • Forrest, Ian A.Royal Victoria Infirmary (author)
  • Simpson, A. JohnUniversity of Newcastle upon Tyne,Royal Victoria Infirmary (author)
  • Gibbons, Michael A.University of Exeter (author)
  • Maher, Toby M.University of Southern California,Royal Brompton and Harefield NHS Foundation Trust,Imperial College London (author)
  • University of EdinburghGalecto Biotech ApS, Denmark (creator_code:org_t)

Related titles

  • In:European Respiratory Journal: European Respiratory Society (ERS)57:50903-19361399-3003

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