Rheumatology Advance Access originally published online on June 15, 2004
Rheumatology 2004 43(9):1097-1105; doi:10.1093/rheumatology/keh254
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Rheumatology Vol. 43 No. 9 © British Society for Rheumatology 2004; all rights reserved
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Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX
Department of Hematology, Oncology and Rheumatology, Clinic for Internal Medicine V, University of Heidelberg and Centre of Rheumatic Diseases, Baden-Baden, 1 Division of Rheumatology and Clinical Immunology, Department of Internal Medicine I, University of Regensburg, Germany, 2 WHO Collaborating Center for Molecular Biology and Novel Therapeutic Strategies for Rheumatic Diseases, University of Zürich, Switzerland, 3 Department of Radiochemistry and Radiopharmacology (E0300), German Cancer Research Center (DKFZ), Heidelberg and 4 Center for Molecular Imaging, Department of Neurology, University of Regensburg, Germany.
Correspondence to: U. Müller-Ladner, Department of Internal Medicine I, University of Regensburg, D-93042 Regensburg, Germany. E-mail: ulf.mueller-ladner{at}klinik.uni-r.de
Objective. To evaluate the anti-arthritic effects of the new inflammation-targeted drug MTX-HSA and to investigate whether peripheral blood mononuclear cells (PBMC) are potential target cells for albumin-mediated drug delivery.
Methods. The murine model of collagen-induced arthritis (CIA) was used to measure the anti-arthritic effect of MTX, MTX-HSA or a combination of both (n = 30 to 35 per group). In addition, the uptake of fluorescence-labelled albumin (AFLc-HSA) in PBMC of 14 patients with RA was measured by fluorescence-activated cell sorting (FACS).
Results. In equivalent doses of 7.5 mg/kg intravenously (IV) twice a week, MTX-HSA is significantly (P<0.02) superior to MTX in inhibiting the development of CIA and reducing the joint count as well as the number of affected paws. When given in lower doses as combination therapy, both drugs act synergistically (P<0.03). A mean of 96, 72 and 64% of the CD14-, CD16- and CD20-positive cells from peripheral blood of rheumatoid arthritis (RA) patients showed an uptake of albumin after incubation with AFLc-HSA in vitro. This finding was not significantly different in comparison to healthy controls. In contrast, the number of CD3-positive cells taking up albumin is increased significantly in RA patients in comparison to controls (26.3 ± 12.9% S.D. vs 11.6 ± 7.3% S.D.; P = 0.005).
Conclusion. The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically. In addition, albumin appears to be taken up by peripheral blood cells, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach.
KEY WORDS: Methotrexate, Rheumatoid arthritis, Albumin, T lymphocytes, Macrophages
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