Objective: ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the development of osteoarthritis (OA), by use of several mouse mutants carrying either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant aggrecan. We have selected recombinant monoclonal antibodies directed against ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017 revealed very high affinity for the enzyme in Biacore analyses and very good specificity in a panel of binding assays. Therefore, we tested CRB0017 in a relevant spontaneous OA model, the STR/ort mouse. Design: STR/ort male mice were recruited at 5 months of age, and treated intra-articularly in each knee with CRB0017 1.2μg, CRB0017 12μg, or vehicle. After 6 weeks, the intra-articular administration of CRB0017 was repeated with the same doses. After 3 months from recruitment, the animals were sacrificed and the femorotibial joints processed for histology and scored in a blind fashion according to both Mankin's and the OARSI methods. Results and conclusions: All histological scores were significantly decreased in the CRB0017 12μg/knee group compared to vehicle, while administration of CRB0017 1.2μg was associated with a trend to a decrease in the same parameters. Therefore, CRB0017 administered twice in 3 months could modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as assessed histologically. The procedure of blind scoring of the histological samples clearly showed that knee intra-articular administration of CRB0017, an anti-ADAMTS5 antibody, dose-dependently improved disease progression in a relevant animal model of OA. © 2013 Osteoarthritis Research Society International.

Chiusaroli, R., Visentini, M., Galimberti, C., Casseler, C., Mennuni, L., Covaceuszach, S., et al. (2013). Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis. OSTEOARTHRITIS AND CARTILAGE, 21(11), 1807-1810 [10.1016/j.joca.2013.08.015].

Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis

Galimberti C.;
2013

Abstract

Objective: ADAMTS5 (aggrecanase-2) has been demonstrated to be crucial in the development of osteoarthritis (OA), by use of several mouse mutants carrying either truncated, catalytically inactive enzymes or aggrecanase-resistant mutant aggrecan. We have selected recombinant monoclonal antibodies directed against ADAMTS5, by using Intracellular Antibody Capture Technology (IACT). CRB0017 revealed very high affinity for the enzyme in Biacore analyses and very good specificity in a panel of binding assays. Therefore, we tested CRB0017 in a relevant spontaneous OA model, the STR/ort mouse. Design: STR/ort male mice were recruited at 5 months of age, and treated intra-articularly in each knee with CRB0017 1.2μg, CRB0017 12μg, or vehicle. After 6 weeks, the intra-articular administration of CRB0017 was repeated with the same doses. After 3 months from recruitment, the animals were sacrificed and the femorotibial joints processed for histology and scored in a blind fashion according to both Mankin's and the OARSI methods. Results and conclusions: All histological scores were significantly decreased in the CRB0017 12μg/knee group compared to vehicle, while administration of CRB0017 1.2μg was associated with a trend to a decrease in the same parameters. Therefore, CRB0017 administered twice in 3 months could modify the course of OA in the STR/ort mouse, by delaying cartilage breakdown as assessed histologically. The procedure of blind scoring of the histological samples clearly showed that knee intra-articular administration of CRB0017, an anti-ADAMTS5 antibody, dose-dependently improved disease progression in a relevant animal model of OA. © 2013 Osteoarthritis Research Society International.
Articolo in rivista - Articolo scientifico
ADAMTS5; Animal model; Monoclonal antibody; Osteoarthritis; STR/ort mouse; ADAM Proteins; ADAMTS5 Protein; Animals; Antibodies, Monoclonal; Arthritis, Experimental; Disease Progression; Drug Administration Schedule; Drug Evaluation, Preclinical; Injections, Intra-Articular; Male; Mice; Mice, Inbred Strains; Osteoarthritis; Recombinant Proteins;
English
2013
21
11
1807
1810
open
Chiusaroli, R., Visentini, M., Galimberti, C., Casseler, C., Mennuni, L., Covaceuszach, S., et al. (2013). Targeting of ADAMTS5's ancillary domain with the recombinant mAb CRB0017 ameliorates disease progression in a spontaneous murine model of osteoarthritis. OSTEOARTHRITIS AND CARTILAGE, 21(11), 1807-1810 [10.1016/j.joca.2013.08.015].
File in questo prodotto:
File Dimensione Formato  
(2013) Targeting of ADAMTS-5’s ancillary domain with the recombinant mAb CRB0017 (Chiusaroli) OsteoarthrCart 2013.pdf

accesso aperto

Descrizione: Articolo
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 1.16 MB
Formato Adobe PDF
1.16 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/320680
Citazioni
  • Scopus 47
  • ???jsp.display-item.citation.isi??? 44
Social impact