A hyaluronic acid–methotrexate conjugate for targeted therapy of rheumatoid arthritis

2014 ◽  
Vol 50 (57) ◽  
pp. 7632 ◽  
Author(s):  
Jung Min Shin ◽  
Seol-Hee Kim ◽  
Thavasyappan Thambi ◽  
Dong Gil You ◽  
Jueun Jeon ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Therapy

scholarly journals Hyaluronic Acid Coated Acid-Sensitive Nanoparticles for Targeted Therapy of Adjuvant-Induced Arthritis in Rats

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 146 ◽  
Author(s):  
Changhui Yu ◽  
Xiangyu Li ◽  
Yufei Hou ◽  
Xiangxue Meng ◽  
Deli Wang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Therapy ◽  
Zeta Potential ◽  
Polymeric Nanoparticles ◽  
Vital Role ◽  
Activated Macrophages ◽  
Acid Sensitivity ◽  
Adjuvant Induced Arthritis

Activated macrophages play a vital role in rheumatoid arthritis (RA) pathophysiology. CD44 is an overexpressed receptor on activated macrophages that is a potential target site for RA treatment. In this study, we prepared hyaluronic acid (HA) coated acid-sensitive polymeric nanoparticles (HAPNPs) composed of egg phosphatidylcholine, polyethylenimine, and poly (cyclohexane-1,4-diyl acetone dimethylene ketal) (PCADK) loaded with dexamethasone (Dex) for the treatment of RA. PCADK was used to form polymeric cores because of its acid-sensitivity. The HAPNPs were about 150 nm in size and had a zeta potential of −2.84 mV. The release rate of Dex from HAPNPs/Dex in vitro increased markedly when the pH decreased from 7.4 to 4.5, indicating that the HAPNPs were pH-sensitive. In a cellular uptake study, stronger fluorescence signals were observed in activated macrophages treated with HAPNPs, suggesting that HAPNPs could be effective nanodevices target to activated macrophages. In rats with adjuvant-induced arthritis, HAPNPs could inhibited the progression of RA. Taken together, these results suggest that the HAPNPs could be useful in RA therapy.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Hyaluronic Acid-Coated MTX-PEI Nanoparticles for Targeted Rheumatoid Arthritis Therapy

Crystals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 321
Author(s):  
Shenghui Zhong ◽  
Peng Liu ◽  
Jinsong Ding ◽  
Wenhu Zhou
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Targeted Delivery ◽  
High Dose ◽  
One Pot ◽  
Inflammatory Site ◽  
Pei Nanoparticles ◽  
Toxic Reactions

Methotrexate (MTX) is an anchor drug for the treatment of rheumatoid arthritis (RA); however, long-term and high-dose usage of MTX for patients can cause many side effects and toxic reactions. To address these difficulties, selectively delivering MTX to the inflammatory site of a joint is promising in the treatment of RA. In this study, we prepared MTX-PEI@HA nanoparticles (NPs), composed of hyaluronic acid (HA) as the hydrophilic negative electrical shell, and MTX-linked branched polyethyleneimine (MTX-PEI) NPs as the core. MTX-PEI@HA NPs were prepared in the water phase by a one-pot method. The polymeric NPs were selectively internalized via CD44 receptor-mediated endocytosis in the activated macrophages. In the in vivo mice mode study, treatment with MTX-PEI@HA NPs mitigated inflammatory arthritis with notable safety at a high dose of MTX. We highlight the distinct advantages of aqueous-synthesized NPs coated with HA for arthritis-selective targeted delivery, thus verifying MTX-PEI@HA NPs as a promising MTX-based nanoplatform for treatment of RA.

scholarly journals AB0138 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER STRATIFIES SEROPOSITIVE RHEUMATOID ARTHRITIS PATIENTS BASED ON THEIR LIKELIHOOD OF INADEQUATE RESPONSE TO TNF INHIBITOR THERAPIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1096.3-1097
Author(s):  
S. Cohen ◽  
V. Strand ◽  
E. Connolly-Strong ◽  
J. Withers ◽  
L. Zhang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Molecular Signature ◽  
Inadequate Response ◽  
Tnf Inhibitor ◽  
Odds Ratios ◽  
Selection For ◽  
Necrosis Factor

Background:There is an urgent need for precision medicine in targeted therapy selection for the treatment of rheumatoid arthritis (RA). TNF inhibitor (TNFi) therapies are the most prescribed targeted therapy for RA patients, yet the majority of patients fail to achieve a clinically meaningful response using this medication class. A blood-based molecular signature test evaluates RNA and clinical metrics to stratify RA patients based on their likelihood of having an inadequate response to TNFi therapies.1 Patients unlikely to respond to TNFi therapies can be directed to a different treatment option such as a JAK inhibitor, thus reducing the time needed to identify an effective therapy, improving confidence in and adherence to treatment, and increasing the patients’ chance of reaching treat-to-target goals.Objectives:High-titers of anti-cyclic citrillunated protein (anti-CCP) have been independently associated with reduced response to TNFi therapy;2 thus, we evaluated the ability of a blood-based molecular signature response classifier (MSRC) test to stratify RA patients by their likelihood of inadequate response to TNFi therapies – regardless of their positive or negative anti-CCP status.Methods:A subset of patients enrolled in the Network-04 prospective observational trial evaluating the ability of a molecular signature response classifier to stratify patients were subdivided into two groups based upon whether they were positive (N = 72) or negative (N = 74) for anti-CCP. The odds of inadequate response to TNFi therapies were calculated based on whether or not a patient had a molecular signature of non-response to TNFi therapy at baseline before the start of treatment. Odds ratios and confidence intervals were calculated3,4 to represent the strength of association between detecting the molecular signature of non-response and the patient’s failure to achieve ACR50 at 6 months.Results:The odds that a patient with a molecular signature of non-response failed to meet ACR50 criteria at 6 months was approximately three times greater than among those patients who lacked the signal (Table 1). No significant difference in odds ratios was observed between patients who were positive or negative for anti-CCP.Table 1.The odds of patients with a molecular signature of non-response failing to achieve an ACR50 response 6 months after TNF inhibitor therapy initiationOdds ratio (95% confidence interval)Anti-CCP positive3.5 (1.3-9.7)Anti-CCP negative3.1 (1.2-8.3)Conclusion:The MSRC test evaluates RA disease biology and accurately stratifies patients based on their likelihood of having an inadequate response to TNFi therapies, regardless of being negative or positive for anti-CCP autoantibodies. Rheumatologists can use the results of the MSRC test to inform targeted therapy selection for RA patients, instead of their anti-CCP serostatus, eliminating the variability inherent to the anti-CCP measurement and its inability to consistently predict TNFi therapy incompatibility. With the MSRC test, providers can rely on a more predictable and accurate assessment of TNFi therapy success or failure when coordinating patient management.References:[1]Mellors, T. et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine3, 91-104, doi:10.1089/nsm.2020.0007 (2020).[2]Braun-Moscovici, Y. et al. Anti-cyclic citrullinated protein antibodies as a predictor of response to anti-tumor necrosis factor-alpha therapy in patients with rheumatoid arthritis. J Rheumatol33, 497-500 (2006).[3]Szumilas, M. Explaining odds ratios. J Can Acad Child Adolesc Psychiatry19, 227-229 (2010).[4]Sperandei, S. Understanding logistic regression analysis. Biochem Med (Zagreb) 24, 12-18, doi:10.11613/BM.2014.003 (2014).Disclosure of Interests:Stanley Cohen: None declared, Vibeke Strand Consultant of: Abbvie, Amgen, Arena, BMS, Boehringer Ingelheim, Celltrion, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen,Kiniksa, Lilly,Merck, Novartis, Pfizer, Regeneron, Samsung, Sandoz, Sanofi, Setpoint, UCB, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

S1P-targeted therapy for elderly rheumatoid arthritis patients with osteoporosis

2010 ◽  
Vol 31 (7) ◽  
pp. 967-969 ◽  
Author(s):  
Junichi Kikuta ◽  
Kaori Iwai ◽  
Yukihiko Saeki ◽  
Masaru Ishii
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy

scholarly journals Rheumatoid Arthritis: Hyaluronic Acid and Cartilage Oligomeric Matrix Protein as Predictors of the Disease Progression

2016 ◽  
Vol 9 (1) ◽  
pp. 15-23
Author(s):  
SAID AL-DALAEN ◽  
AIMAN AL-QTAITAT ◽  
MOHAMMAD AL-RAWASHDEH ◽  
JIHAD ALZYOUD ◽  
AIMAN AL-MAATHADI
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Disease Progression ◽  
Cartilage Oligomeric Matrix Protein ◽  
Matrix Protein ◽  
And Cartilage

B Cell-Targeted Therapy for Rheumatoid Arthritis

Drugs ◽  
2006 ◽  
Vol 66 (5) ◽  
pp. 625-639 ◽  
Author(s):  
R John Looney
Keyword(s):  
Rheumatoid Arthritis ◽  
Targeted Therapy ◽  
B Cell
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