Author

Bing He

Year of Award

2016

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

School of Chinese Medicine.Teaching and Research Division.;Hong Kong Baptist Universtiy.

Principal Supervisor

Lü, Aiping

Keywords

Alternative treatment;Blood proteins;Chemotherapy, Combination;Drug interactions;Leflunomide;Rheumatoid arthritis;Side effects

Language

English

Abstract

Leflunomide is widely prescribed for Rheumatoid Arthritis (RA) patients in China. However, a number of RA patients still demonstrated progressive bone erosion (PBE+) after receiving Leflunomide in our clinical data. Moreover, the PBE+ is predicted by high baseline serum CRP level (CRPBH). Further, the changes of serum bone resorption marker (Tartrate-resistant acid phosphatase 5b, TRAP5b) strongly correlated with those of CRP in PBE+ RA patients during Leflunomide treatment. Those were consistently observed in collagen-induced-arthritis (CIA) rats. To precisely address the issue, we screened a series of marketed drugs combined with Leflunomide to inhibit CRP production and CRP-related osteoclastic signaling pathway using bioinformatics analysis. Ligustrazine was postulated as an optimal candidate drug. In vitro studies demonstrated that the combination of Ligustrazine and Leflunomide not only suppressed hepatic CRP production, but also suppressed CRP-related osteoclastic signaling and osteoclast activities. In vivo studies showed that the combination attenuated bone erosion in CIA rats. Further, the randomized parallel controlled clinical trial in 120 CRPBH RA patients showed that the combination therapy reduced serum CRP levels and attenuated bone erosion in those patients (ChiCTR-TRC-10001014). Together, this work presents a precision combination therapy for PBE+ in CRPBH RA patients.

Comments

Principal supervisor: Dr. Lu Aiping.;Thesis submitted to the School of Chinese Medicine, Teaching and Research Division.;Thesis (Ph.D.)--Hong Kong Baptist University, 2016.;

Bibliography

Includes bibliographical references (pages 115-128)

Available for download on Tuesday, February 27, 2018


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