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Kazuhito Kawabata - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.
    International journal of rheumatology, 2019
    Co-Authors: Hiroyuki Yamada, Hiroshi Mori, Yasutomo Nakanishi, Satoshi Nishikawa, Yasuaki Hashimoto, Yasuo Ochi, Makoto Tanaka, Kazuhito Kawabata
    Abstract:

    We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by Collagen-Induced Arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this Collagen-Induced Arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p

Berit Johansen - One of the best experts on this subject based on the ideXlab platform.

  • cytosolic group iva phospholipase a2 inhibitors avx001 and avx002 ameliorate collagen induced Arthritis
    Arthritis Research & Therapy, 2019
    Co-Authors: Astrid Jullumstro Feuerherm, Edward A Dennis, Berit Johansen
    Abstract:

    Background Cytosolic phospholipase A2 group IVA (cPLA2α)-deficient mice are resistant to Collagen-Induced Arthritis, suggesting that cPLA2α is an important therapeutic target. Here, the anti-inflammatory effects of the AVX001 and AVX002 cPLA2α inhibitors were investigated.

  • Cytosolic group IVA phospholipase A2 inhibitors, AVX001 and AVX002, ameliorate Collagen-Induced Arthritis
    BMC, 2019
    Co-Authors: Astrid Jullumstro Feuerherm, Edward A Dennis, Berit Johansen
    Abstract:

    Abstract Background Cytosolic phospholipase A2 group IVA (cPLA2α)-deficient mice are resistant to Collagen-Induced Arthritis, suggesting that cPLA2α is an important therapeutic target. Here, the anti-inflammatory effects of the AVX001 and AVX002 cPLA2α inhibitors were investigated. Methods In vitro enzyme activity was assessed by a modified Dole assay. Effects on inhibiting IL-1β-induced release of arachidonic acid (AA) and prostaglandin E2 (PGE2) were measured using SW982 synoviocyte cells. In vivo effects were studied in prophylactic and therapetic murine Collagen-Induced Arthritis models and compared to methotrexate (MTX) and Enbrel, commonly used anti-rheumatic drugs. The in vivo response to treatment was evaluated in terms of the Arthritis index (AI), histopathology scores and by plasma levels of PGE2 following 14 and 21 days of treatment. Results Both cPLA2α inhibitors are potent inhibitors of cPLA2α in vitro. In synoviocytes, AVX001 and AVX002 reduce, but do not block, release of AA or PGE2 synthesis. In both CIA models, the AI and progression of Arthritis were significantly lower in the mice treated with AVX001, AVX002, Enbrel and MTX than in non- treated mice. Several histopathology parameters of joint damage were found to be significantly reduced by AVX001 and AVX002 in both prophylactic and therapeutic study modes; namely articular cavity and peripheral tissue inflammatory cell infiltration; capillary and synovial hyperplasia; articular cartilage surface damage; and periostal and endochondral ossification. In comparison, MTX did not significantly improve any histopathology parameters and Enbrel only improved ossification. Finally, as a biomarker of inflammation and as an indication that AVX001 and AVX002 blocked the cPLA2α target, we determined that plasma levels of PGE2 were significantly reduced in response to the AVX inhibitors and MTX, but not Enbrel. Conclusions AVX001 and AVX002 display potent anti-inflammatory activity and disease-modifying properties in cellular and in vivo models. The in vivo effects of AVX001 and AVX002 were comparable to, or superior, to those of MTX and Enbrel. Taken together, this study suggests that cPLA2α inhibitors AVX001 and AVX002 are promising small molecule disease-modifying anti-rheumatic therapies

Hiroyuki Yamada - One of the best experts on this subject based on the ideXlab platform.

  • Effects of the Cathepsin K Inhibitor ONO-5334 and Concomitant Use of ONO-5334 with Methotrexate on Collagen-Induced Arthritis in Cynomolgus Monkeys.
    International journal of rheumatology, 2019
    Co-Authors: Hiroyuki Yamada, Hiroshi Mori, Yasutomo Nakanishi, Satoshi Nishikawa, Yasuaki Hashimoto, Yasuo Ochi, Makoto Tanaka, Kazuhito Kawabata
    Abstract:

    We examined whether the cathepsin K inhibitor, ONO-5334, administered alone or in combination with methotrexate (MTX), could ameliorate joint destruction evoked by Collagen-Induced Arthritis (CIA) in female cynomolgus monkeys. CIA was induced by immunizing with bovine type II collagen. ONO-5334 (30 mg/kg/day) was orally administered once daily and MTX (10 mg/body/day) twice weekly for 9 weeks. X-ray (evaluation of joint destruction) and swelling (inflammatory) scores of proximal interphalangeal (PIP), distal interphalangeal (DIP), and metacarpophalangeal (MP) joints were evaluated. Urinary concentrations of C-terminal telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) were measured. Arthritis, accompanied by bone and cartilage destruction, was successfully induced in this Collagen-Induced Arthritis monkey model. ONO-5334 showed no suppressive effect on joint swelling, while the joint swelling scores in the MTX and combination (ONO-5334 + MTX) groups were less than 50% compared with the control group. ONO-5334 decreased X-ray score by a mean of 64% (p

Zheng Chen - One of the best experts on this subject based on the ideXlab platform.

  • Ultrasound remission can predict future good structural outcome in Collagen-Induced Arthritis rats
    Scientific Reports, 2019
    Co-Authors: Wenxue Li, Yiqun Liu, Jiaan Zhu, Arong Bilig, Fang Liu, Zheng Chen
    Abstract:

    Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. The present study aims to explore whether ultrasound remission has predictive value and ultrasound remission at which time point has predictive value for good structural outcome. Collagen-Induced Arthritis (CIA) was induced in 32 rats by immunizing with bovine type II collagen. Twenty-four CIA rats were treated with rhTNFR:Fc, and 8 rats were left untreated. Ultrasonography was performed to assess synovial hypertrophy, power Doppler (PD) signal, and bone erosion of the ankle joints of both hindpaws every week following the booster immunization. In the treated group, the scores for synovial hypertrophy, PD signal and bone erosions decreased from baseline to the end. Synovial hypertrophy, PD signal, and bone erosion at baseline were not significantly associated with good structural outcome. Ultrasound remission from 4 to 6 weeks after treatment was significantly associated with good outcome and had the highest area under the curve, sensitivity, specificity, and positive and negative predictive values. Therefore, we conclude that ultrasound remission from 4 to 6 weeks after treatment has a high value for predicting good structural outcome in CIA rats.

I. Colorado - One of the best experts on this subject based on the ideXlab platform.