Fiehn, C. and Mueller-Ladner, Ulf and Gay, S. and Krienke, S. and Freudenberg-Konrad, S. and Funk, J. and Ho, A. D. and Sinn, H. and Wunder, A. (2004) Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX. RHEUMATOLOGY, 43 (9). pp. 1097-1105. ISSN 1462-0324, 1462-0332
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RHEUMATOID-ARTHRITIS PATIENTS; COLLAGEN-INDUCED ARTHRITIS; PLACEBO-CONTROLLED TRIAL; LOW-DOSE METHOTREXATE; DOUBLE-BLIND; II COLLAGEN; PHARMACOKINETICS; METABOLISM; ANTIBODY; THERAPY; methotrexate; rheumatoid arthritis; albumin; T lymphocytes; macrophages |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jun 2021 09:07 |
| Last Modified: | 30 Jun 2021 09:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37299 |
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