Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat.

Slides:

Advertisements

Similar presentations

Efficacy of ultrasound therapy for the management of knee osteoarthritis: a systematic review with meta-analysis A. Loyola-Sánchez, J. Richardson, N.J.

Advertisements

“A Fully Caninised Anti-NGF Monoclonal Antibody for Pain Relief in Dogs” Scientific Paper Presentation Madeline Jackson Gearing, D. P., Virtue,

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced.

C. R. Flannery, N. Moran, D. Blasioli, K. Donahue, J. Kane, T

Electrical stimulation for pain relief in knee osteoarthritis: systematic review and network meta-analysis C. Zeng, H. li, T. Yang, Z.-h. Deng, Y. Yang,

Multiple injections of platelet rich plasma releasate reduce pain and synovial thickening in a mice osteoarthritis model S. Khatab, G.M. van Buul, P.K.

Pharmacological interrogation of a rodent forced ambulation model: leveraging gait impairment as a measure of pain behavior pre-clinically B.L. Adams,

Single intra-articular injection of adeno-associated virus results in stable and controllable in vivo transgene expression in normal rat knees K.A. Payne,

Reduction of total IgE by targeted coengagement of IgE B-cell receptor and FcγRIIb with Fc-engineered antibody Seung Y. Chu, PhD, Holly M. Horton, PhD,

Comparing intra-articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model E.G. Yarmola, Y.Y. Shah, H.E. Kloefkorn,

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium J.-I. Chung, S. Barua, B.H. Choi,

Monosodium iodoacetate-induced inflammation and joint pain are reduced in TRPA1 deficient mice – potential role of TRPA1 in osteoarthritis L.J. Moilanen,

Dissecting the contribution of knee joint NGF to spinal nociceptive sensitization in a model of OA pain in the rat D.R. Sagar, L. Nwosu, D.A. Walsh,

Electrical stimulation for pain relief in knee osteoarthritis: systematic review and network meta-analysis C. Zeng, H. li, T. Yang, Z.-h. Deng, Y. Yang,

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced.

Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis H. Iijima,

Changes of early post-traumatic osteoarthritis in an ovine model of simulated ACL reconstruction are associated with transient acute post-injury synovial.

Inhibition of cyclooxygenase 2 expression by diallyl sulfide on joint inflammation induced by urate crystal and IL-1β H.-S. Lee, M.D., Ph.D., C.-H. Lee,

Paradoxical effects of the cannabinoid CB2 receptor agonist GW on rat osteoarthritic knee joint pain N. Schuelert, C. Zhang, A.J. Mogg, L.M. Broad,

K. Koda, K. Hyakkoku, K. Ogawa, K. Takasu, S. Imai, Y. Sakurai, M

NF-κBp65-specific siRNA inhibits expression of genes of COX-2, NOS-2 and MMP-9 in rat IL-1β-induced and TNF-α-induced chondrocytes Dr C. Lianxu, Ph.D.,

Spinal nociceptive reflexes are sensitized in the monosodium iodoacetate model of osteoarthritis pain in the rat S. Kelly, K.L. Dobson, J. Harris Osteoarthritis.

Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production M. Hashizume, M. Mihara Osteoarthritis and.

In vivo imaging of MMP-13 activity in the murine destabilised medial meniscus surgical model of osteoarthritis N.H. Lim, E. Meinjohanns, M. Meldal, G.

L.N. Nwosu, P.I. Mapp, V. Chapman, D.A. Walsh

S. Ogawa, Y. Awaga, M. Takashima, A. Hama, A. Matsuda, H. Takamatsu

M. Akagi, M. D. , Ph. D. , A. Ueda, M. D. , T. Teramura, Ph. D. , S

Subchondral plate porosity colocalizes with the point of mechanical load during ambulation in a rat knee model of post-traumatic osteoarthritis H. Iijima,

Comparison of the chondrosarcoma cell line SW1353 with primary human adult articular chondrocytes with regard to their gene expression profile and reactivity.

Deficits in spontaneous burrowing behavior in the rat bilateral monosodium iodoacetate model of osteoarthritis: an objective measure of pain-related behavior.

K. Koda, K. Hyakkoku, K. Ogawa, K. Takasu, S. Imai, Y. Sakurai, M

Increase in excitatory amino acid concentration and transporters expression in osteoarthritic knees of anterior cruciate ligament transected rabbits

J. J. McDougall, S. Albacete, N. Schuelert, P. G. Mitchell, C. Lin, J

Surgically induced osteoarthritis in the rat results in the development of both osteoarthritis-like joint pain and secondary hyperalgesia S.E. Bove,

Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor P.S. Chockalingam, W. Sun, M.A. Rivera-Bermudez,

N. Brandl, A. Zemann, I. Kaupe, S. Marlovits, P. Huettinger, H

Anti-inflammatory effect of low intensity ultrasound (LIUS) on complete Freund's adjuvant-induced arthritis synovium J.-I. Chung, S. Barua, B.H. Choi,

Sustained efficacy of a single intra-articular dose of FX006 in a rat model of repeated localized knee arthritis A. Kumar, A.M. Bendele, R.C. Blanks,

Injury of primary afferent neurons may contribute to osteoarthritis induced pain: an experimental study using the collagenase model in rats S. Adães,

Blockade of nociceptive sensory afferent activity of the rat knee joint by the bradykinin B2 receptor antagonist fasitibant A. Gomis, S. Meini, A. Miralles,

Spontaneous firing in C-fibers and increased mechanical sensitivity in A-fibers of knee joint-associated mechanoreceptive primary afferent neurones during.

Intra-articular anaesthesia mitigates established pain in experimental osteoarthritis: a preliminary study of gait impulse redistribution as a biomarker.

Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: its role in terminal differentiation of chondrocytes in rat and human

Pre-operative interventions (non-surgical and non-pharmacological) for patients with hip or knee osteoarthritis awaiting joint replacement surgery – a.

Pharmacological effects of novel cross-linked hyaluronate, Gel-200, in experimental animal models of osteoarthritis and human cell lines K. Yoshioka,

G. Venne, S. Pang, Y. Tse, R. Ellis Osteoarthritis and Cartilage

Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-κBp65-specific siRNA L.X. Chen, Ph.D., L. Lin,

Measuring and realizing the translational significance of preclinical in vivo studies of painful osteoarthritis M. Hummel, G.T. Whiteside Osteoarthritis.

The anti-NGF antibody muMab 911 both prevents and reverses pain behaviour and subchondral osteoclast numbers in a rat model of osteoarthritis pain L.

Comparing intra-articular CTXII levels assessed via magnetic capture or lavage in a rat knee osteoarthritis model E.G. Yarmola, Y.Y. Shah, H.E. Kloefkorn,

Exercise intervention increases expression of bone morphogenetic proteins and prevents the progression of cartilage-subchondral bone lesions in a post-traumatic.

M.Z.C. Ruan, R.M. Patel, B.C. Dawson, M.-M. Jiang, B.H.L. Lee

Resistin is elevated following traumatic joint injury and causes matrix degradation and release of inflammatory cytokines from articular cartilage in.

Deletion of 12/15-lipoxygenase accelerates the development of aging-associated and instability-induced osteoarthritis L. Habouri, F.E. El Mansouri, Y.

Development of a novel antibody to calcitonin gene-related peptide for the treatment of osteoarthritis-related pain R.J. Benschop, E.C. Collins, R.J.

Therapeutic effects of an anti-ADAMTS-5 antibody on joint damage and mechanical allodynia in a murine model of osteoarthritis R.E. Miller, P.B. Tran,

Dr J. Deschner, D. M. D. , Ph. D. , Dr B. Rath-Deschner, D. M. D. , Ph

K.H. Collins, R.A. Reimer, R.A. Seerattan, T.R. Leonard, W. Herzog

Effect of muscle weakness and joint inflammation on the onset and progression of osteoarthritis in the rabbit knee C. Egloff, A. Sawatsky, T. Leonard,

Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions

Efficacy of low frequency pulsed subsensory threshold electrical stimulation vs placebo on pain and physical function in people with knee osteoarthritis:

Identification and pharmacological characterization of a novel inhibitor of autotaxin in rodent models of joint pain K. Thirunavukkarasu, C.A. Swearingen,

Osteoarthritis and Cartilage

Multiple injections of platelet rich plasma releasate reduce pain and synovial thickening in a mice osteoarthritis model S. Khatab, G.M. van Buul, P.K.

C. R. Flannery, N. Moran, D. Blasioli, K. Donahue, J. Kane, T

Weight bearing as a measure of disease progression and efficacy of anti-inflammatory compounds in a model of monosodium iodoacetate-induced osteoarthritis

A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip or knee T.J. Schnitzer, J.A. Marks Osteoarthritis.

Intra-articular injections of hyaluronan solutions of different elastoviscosity reduce nociceptive nerve activity in a model of osteoarthritic knee joint.

Measurement of synovial fluid volume using urea

Volume 17, Issue 1, Pages (January 2009)

Presentation transcript:

Long-term analgesic effect of a single dose of anti-NGF antibody on pain during motion without notable suppression of joint edema and lesion in a rat model of osteoarthritis G. Ishikawa, Y. Koya, H. Tanaka, Y. Nagakura Osteoarthritis and Cartilage Volume 23, Issue 6, Pages 925-932 (June 2015) DOI: 10.1016/j.joca.2015.02.002 Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Confirmation of binding of AS2886401-00 to rat β-NGF. Binding activities of AS2886401-00 and isotype control IgG to rat β-NGF detected using ELISA-based assay. Data are presented as each replicate from duplicate experiments. Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Increasing cytosolic calcium influx by rat β-NGF and inhibition by AS2886401-00. Cytosolic calcium concentration increase in human TrkA expressed in HEK293 cells by rat β-NGF detected using FLIPR (A). Cytosolic calcium influx inhibition by AS2886401-00, with 40 and 150 ng/mL rat β-NGF used as stimulator (B). Antibody concentration range from 0.01 to 1 μg/mL. Data are presented as each replicate from duplicate experiments. Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 In vivo pharmacokinetic profile of AS2886401-00. AS2886401-00 was intravenously administered to rats, and plasma samples were drawn at indicated time points. Plasma concentration of AS2886401-00 was measured using an ELISA-based method. The points on each graph represent the mean ± S.D. for three rats. Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Long-lasting effect of a single administration of AS2886401-00 on the imbalance in max contact area (A) and swing speed (B) measured by gait analysis paradigm in MIA-induced arthritis rats. Imbalances in max contact area and swing speed immediately developed following MIA administration and were sustained during the experimental period (open squares). AS2886401-00 was intravenously administered on Day 3 post-MIA administration. Data represent the difference between ipsilateral and contralateral hind limb and are presented as mean ± S.D. (n = 12 for 0.1 or 1 mg/kg of AS2886401-00, n = 11 for 0.3 mg/kg of AS2886401-00, n = 12 for vehicle and n = 10 for sham). Statistical comparison was performed on Day 35. ∗∗∗P < 0.001 compared to corresponding vehicle (Dunnett's multiple comparison test). Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 5 Influence of timing of intervention with AS2886401-00 on analgesic outcome. Imbalance in max contact area (left) and swing speed (right) was measured by the gait analysis paradigm in MIA-induced arthritis rats. AS2886401-00 was intravenously administered 1 h (A, E) (n = 10 per group), 24 h (B, F) (n = 10 per group), 7 days (C, G) (n = 10 per group) or 18 days (D, H) (n = 12 for 0.1 or 1 mg/kg of AS2886401-00, n = 11 for 0.3 mg/kg of AS2886401-00, n = 12 for vehicle and n = 10 for sham) prior to gait measurement (i.e., efficacy evaluation) which was conducted at Week 3 post-MIA administration. Data represent the difference between ipsilateral and contralateral hind limb and are presented as mean ± S.D. ∗P < 0.05, ∗∗P < 0.01, and ∗∗∗P < 0.001 compared to corresponding vehicle control (Dunnett's multiple comparison test). +++P < 0.001 compared to corresponding sham control (Student's t test). Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions

Fig. 6 Effect of AS2886401-00 on knee diameter (A) and knee lesion score (B) in rats with MIA-induced arthritis. Knee diameter on Day 35 post-MIA administration was assessed (n = 7 for each AS2886401-00 dose, n = 7 for vehicle and n = 5 for sham). The differences in the diameter between the right and left knee were determined by subtracting the values of the left side from those of right (MIA-injected side). Data are presented as mean ± S.D. ∗∗∗P < 0.001 compared to vehicle-treated MIA rats (Dunnett's multiple comparison test). +P < 0.05 compared to sham control rats (Student's t test) (A). The ipsilateral tibias were removed on Day 35 post-MIA administration. The score of each tibia was defined as the mean scores of two independent observers. Each circle indicates the score in each individual. The bar represents the median of scores in each group (n = 12 for 0.1 or 1 mg/kg of AS2886401-00 dose, n = 11 for 0.3 mg/kg of AS2886401-00, n = 12 for vehicle and n = 10 for sham). +++P < 0.001 compared to sham control rats (Wilcoxon rank sum test) (B). Osteoarthritis and Cartilage 2015 23, 925-932DOI: (10.1016/j.joca.2015.02.002) Copyright © 2015 Osteoarthritis Research Society International Terms and Conditions