Disease modifying osteoarthritis drugs: Facing development challenges and choosing molecular targets

Current Drug Targets

Volumn 11, Issue 5, 2010, Pages 528-535

  Hellio Le Graverand Gastineau, Marie Pierre ^a  

^a PFIZER INC   (United States)

Author keywords

DMOADs; Molecular targets; Osteoarthritis; Structural progression

Indexed keywords

CALCITONIN; CATHEPSIN K INHIBITOR; CHONDROITIN SULFATE; COLLAGENASE 3; DIACETYLRHEIN; DISEASE MODIFYING ANTIRHEUMATIC DRUG; DOXYCYCLINE; FIBROBLAST GROWTH FACTOR 18; GLUCOSAMINE SULFATE; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1 RECEPTOR BLOCKING AGENT; INTERLEUKIN 6; LICOFELONE; MATRIX METALLOPROTEINASE INHIBITOR; OSTEOGENIC PROTEIN 1; PIASCLEDINE; RECOMBINANT LUBRICIN; RISEDRONIC ACID; SALCATONIN; STROMELYSIN; TISSUE INHIBITOR OF METALLOPROTEINASE 1; TISSUE INHIBITOR OF METALLOPROTEINASE 2; TISSUE INHIBITOR OF METALLOPROTEINASE 3; TISSUE INHIBITOR OF METALLOPROTEINASE 4; TUMOR NECROSIS FACTOR ALPHA INHIBITOR; UNCLASSIFIED DRUG; VITAMIN D;

ARTHRALGIA; ARTICULAR CARTILAGE; CLINICAL TRIAL; DISEASE COURSE; DISEASE SEVERITY; DRUG SAFETY; HIP OSTEOARTHRITIS; HUMAN; JOINT CAPSULE; JOINT RADIOGRAPHY; KNEE MENISCUS; KNEE OSTEOARTHRITIS; NONHUMAN; REVIEW; SYNOVIUM; TREATMENT OUTCOME;

ANABOLIC AGENTS; ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; HUMANS; METABOLISM; OSTEOARTHRITIS;

EID: 77951051360     PISSN: 13894501     EISSN: None     Source Type: Journal    
DOI: 10.2174/138945010791011893     Document Type: Review

References (62)

1. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arthritis Rheum 1998; 43: 778-799
2. Hellio Le Graverand-Gastineau MP. OA clinical trials: current targets and trials for OA. Choosing molecular targets: what have we learned and where we are headed? Osteoarthritis Cartilage 2009; 17(11): 1393-1401
3. CPMP Points to Consider - Clinical Investigation of Medicinal Products Used in the Treatment of OA - 7/98.
4. FDA - Clinical Development Programs for Drugs, Devices and Biological Products Intended for the Treatment of OA - 7/99. http://www.fda.gov/Cber/gdlns/ osteo.htm
5. Maillefert JF, Gueguen A, Nguyen M, et al. Relevant change in radiological progression in patients with hip osteoarthritis. I. Determination using predictive validity for total hip arthroplasty. Rheumatology (Oxford) 2002; 41: 142-147
6. Brandt KD, Mazzuca SA, Katz BP, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebocontrolled, double-blind trial. Arthritis Rheum 2005; 52: 2015-2025
7. Hellio Le Graverand MP, Vignon EP, et al. Head-to-head comparison of the Lyon Schuss and fixed flexion radiographic techniques. Long-term reproducibility in normal knees and sensitivity to change in osteoarthritic knees. Ann Rheum Dis 2008 Nov; 67(11): 1562-1566
8. Hunter DJ, Le Graverand MP, Eckstein F. Radiologic markers of osteoarthritis progression. Curr Opin Rheumatol 2009; 21(2): 110-117
9. Hellio Le Graverand MP, Buck R, Wyman BT, et al. Change in regional cartilage morphology and joint space width in osteoarthritis participants versus healthy controls - a multicenter study using 3.0 Tesla MRI and Lyon Schuss radiography. Ann Rheum Dis 2010; 69(1): 155-162
10. Hutchinson JW, Tierney GM, Parsons SL, Davis TR. Dupuytren's disease and frozen shoulder induced by treatment with a MMP inhibitor. J Bone Joint Surgery - British Volume 1998; 80: 907-908
11. Johnson AR, Pavlovsky AG, Ortwine DF, et al. Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia. J Biol Chem 2007; 282: 27781-27791
12. Bingham CO 3rd, Buckland-Wright JC, Garnero P, et al. Risedronate decreases biochemical markers of cartilage degradation but does not decrease symptoms or slow radiographic progression in patients with medial compartment osteoarthritis of the knee: results of the two-year multinational knee osteoarthritis structural arthritis study. Arthritis Rheum 2006; 54: 3494-3507 (Pubitemid 44737161)
13. Suri S, Gill SE, Massena de Camin S, Wilson D, McWilliams DF, Walsh DA. Neurovascular invasion at the osteochondral junction and in osteophytes in osteoarthritis. Ann Rheum Dis 2007; 66: 1423-1428 (Pubitemid 350032647)
14. Hellio Le Graverand MP, Sciore P, Eggerer J, et al. Formation and phenotype of cell clusters in osteoarthritic meniscus. Arthritis Rheum 2001; 44: 1808-1818 (Pubitemid 32758228)
15. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA. Early changes in lapine menisci during osteoarthritis development: Part I: cellular and matrix alterations. Osteoarthritis Cartilage 2001; 9: 56-64. (Pubitemid 32154918)
16. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA. Early changes in lapine menisci during osteoarthritis development: Part II: molecular alterations. Osteoarthritis Cartilage 2001; 9: 65-72. (Pubitemid 32154919)
17. Maillefert JF, Hawker GA, Gossec L, et al. Concomitant therapy: an outcome variable for musculoskeletal disorders? Part 2: total joint replacement in osteoarthritis trials. J Rheumatol 2005; 32: 2449-2451 (Pubitemid 41780666)
18. Davis AM, Perruccio AV, Canizares M, et al. The development of a short measure of physical function for hip OA HOOS-Physical Function Shortform (HOOS-PS): an OARSI/OMERACT initiative. Osteoarthritis Cartilage 2008; 16: 551-559
19. Hawker GA, Davis AM, French MR, et al. Development and preliminary psychometric testing of a new OA pain measure - an OARSI/OMERACT initiative. Osteoarthritis Cartilage 2008; 16(4): 409-414
20. Gossec L, Hawker G, Davis AM, et al. OMERACT/OARSI initiative to define states of severity and indication for joint replacement in hip and knee osteoarthritis. J Rheumatol 2007; 34: 1432-1435 (Pubitemid 46898131)
21. Ornetti P, Brandt K, Hellio-Le Graverand MP, et al. OARSIOMERACT definition of relevant radiological progression in hip/knee osteoarthritis. Osteoarthritis Cartilage 2009; 17(7): 842-849
22. Dougados M, Hawker G, Lohmander S, et al. OARSI/OMERACT criteria of being considered a candidate for total joint replacement in knee/hip osteoarthritis as an endpoint in clinical trials evaluating potential disease modifying osteoarthritic drugs. J Rheumatol 2009 Sep; 36(9): 2097-2099
23. Manicourt DH, Altman RD, Williams JM, et al. Treatment with calcitonin suppresses the responses of bone, cartilage, and synovium in the early stages of canine experimental osteoarthritis and significantly reduces the severity of the cartilage lesions. Arthritis Rheum 1999; 42: 1159-1167
24. Karsdal MA, Sondergaard BC, Arnold M, Christiansen C. Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis? Ann N Y Acad Sci 2007; 1117: 181-195
25. Pelletier JP, Jovanovic D, Fernandes JC, et al. Reduced progression of experimental osteoarthritis in vivo by selective inhibition of inducible nitric oxide synthase. Arthritis Rheum 1998; 41: 1275-1286
26. Pelletier JP, Jovanovic D, Fernandes JC, et al. Selective inhibition of iNOS in experimental OA is associated with reduction in tissue levels of catabolic factors. J Rheumatol 1999; 26: 2002-2014
27. Pelletier J-P, Jovanovic DV, Lascau-Coman V, et al. Selective inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo: Possible link with the reduction in chondrocyte apoptosis and caspase 3 level. Arthritis Rheum 2000; 43: 1290-1299
28. Hashimoto S, Takahashi K, Amiel D, Coutts RD, Lotz M. Chondrocyte apoptosis and nitric oxide production during experimentally induced osteoarthritis. Arthritis Rheum 1998; 41: 1266-1274 (Pubitemid 28313430)
29. Hellio Le Graverand MP, Vignon E, Otterness IG, Hart DA. Early changes in lapine menisci during osteoarthritis development Part II: Molecular alterations. Osteoarthritis Cartilage 2000; 9: 65-72. (Pubitemid 32154919)
30. Kobayashi K, Mishima H, Hashimoto S, Goomer RS, Harwood FL, Lotz M. Chondrocyte apoptosis and regional differential expression of nitric oxide in the medial meniscus following partial meniscectomy. J Orthop Res 2001; 19: 802-808 (Pubitemid 32799065)
31. van den Berg WB, van de Loo F, Joosten LA, Arntz OJ. Animal models of arthritis in NOS2-deficient mice. Osteoarthritis Cartilage 1999; 7: 413-415 (Pubitemid 29331565)
32. Downs JT, Lane CL, Nestor NB, et al. Analysis of collagenasecleavage of type II collagen using a neoepitope ELISA. J Immunol Methods 2001; 247: 25-34.
33. Poole AR, Ionescu M, Fitzcharles MA, Billinghurst RC. The assessment of cartilage degradation in vivo: development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases. J Immunol Methods 2004; 294: 145-153
34. Neuhold LA, Killar L, Zhao W, et al. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Invest 2001; 107: 35-44. (Pubitemid 32047412)
35. Baragi VM, Becher G, Bendele AM, et al. A new class of potent matrix metalloproteinase 13 inhibitors for potential treatment of osteoarthritis: Evidence of histologic and clinical efficacy without musculoskeletal toxicity in rat models. Arthritis Rheum 2009; 60(7): 2008-2018
36. Hughes CE, Caterson B, Fosang AJ, Roughley PJ, Mort JS. Monoclonal antibodies that specifically recognize neoepitope sequences generated by 'aggrecanase' and matrix metalloproteinase cleavage of aggrecan: application to catabolism in situ and in vitro. Biochem J 1995; 305: 799-804.
37. van Meurs JB, van Lent PL, Holthuysen AE, Singer II, Bayne EK, van den Berg WB. Kinetics of aggrecanase- and metalloproteinase-induced neoepitopes in various stages of cartilage destruction in murine arthritis. Arthritis Rheum 1999; 42: 1128-1139
38. Glasson SS, Askew R, Sheppard B, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature 2005; 434: 644-648 (Pubitemid 40488556)
39. Majumdar MK, Askew R, Schelling S, et al. Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis. Arthritis Rheum 2007; 56: 3670-3674 (Pubitemid 350100701)
40. Fosang AJ, Little CB. Drug insight: aggrecanases as therapeutic targets for osteoarthritis. Nat Clin Pract Rheumatol 2008; 4: 420-427
41. Tortorella MD, Tomasselli AG, Mathis KJ, et al. Structural and inhibition analysis reveals the mechanism of selectivity of a series of aggrecanase inhibitors. J Biol Chem 2009; 284(36): 24185-24191
42. Nagase H, Brew K. Designing TIMP (tissue inhibitor of metalloproteinases) variants that are selective metalloproteinase inhibitors. Biochem Soc Symp 2003; 70: 201-212
43. Sahebjam S, Khokha R, Mort JS. Increased collagen and aggrecan degradation with age in the joints of Timp3(-/-) mice. Arthritis Rheum 2007; 56: 905-909 (Pubitemid 46399438)
44. Fan Z, Chubinskaya S, Rueger DC, Bau B, Haag J, Aigner T. Regulation of anabolic and catabolic gene expression in normal and osteoarthritic adult human articular chondrocytes by osteogenic protein-1. Clin Exp Rheumatol 2004; 22: 103-106 (Pubitemid 38232816)
45. Chubinskaya S, Hurtig M, Rueger DC. OP-1/BMP-7 in cartilage repair. Int Orthop 2007; 31(6): 773-781
46. Hurtig M, Chubinskaya S, Dickey J, Rueger D. BMP-7 protects against progression of cartilage degeneration after impact injury. J Orthop Res 2009; 27(5): 602-611
47. Hayashi M, Muneta T, Ju YJ, Mochizuki T, Sekiya I. Weekly intraarticular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression. Arthritis Res Ther 2008; 10(5): R118.
48. Badlani N, Inoue A, Healey R, Coutts R, Amiel D. The protective effect of OP-1 on articular cartilage in the development of osteoarthritis. Osteoarthritis Cartilage 2008; 16(5): 600-606 (Pubitemid 351524695)
49. Sekiya I, Tang T, Hayashi M, et al. Periodic knee injections of BMP-7 delay cartilage degeneration induced by excessive running in rats. J Orthop Res 2009; 27(8): 1088-1092
50. Haque T, Nakada S, Hamdy RC. A review of FGF18: Its expression, signaling pathways and possible functions during embryogenesis and post-natal development. Histol Histopathol 2007; 22(1): 97-105. (Pubitemid 46117095)
51. Moore EE, Bendele AM, Thompson DL, et al. Fibroblast growth factor-18 stimulates chondrogenesis and cartilage repair in a rat model of injury-induced osteoarthritis. Osteoarthritis Cartilage 2005; 13(7): 623-631
52. Jones AR, Gleghorn JP, Hughes CE, et al. Binding and localization of recombinant lubricin to articular cartilage surfaces. J Orthop Res 2007; 25: 283-292
53. Flannery CR, Zollner R, Corcoran C, et al. Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin. Arthritis Rheum 2009; 60(3): 840-847
54. Elsaid KA, Fleming BC, Oksendahl HL, et al. Decreased lubricin concentrations and markers of joint inflammation in the synovial fluid of patients with anterior cruciate ligament injury. Arthritis Rheum 2008; 58(6): 1707-1715
55. Spector TD, Conaghan PG, Buckland-Wright JC, et al. Effect of risedronate on joint structure and symptoms of knee osteoarthritis: results of the BRISK randomized, controlled trial. Arthritis Res Ther 2005; 7: 625-633
56. Krzeski P, Buckland-Wright C, Bálint G, et al. Development of musculoskeletal toxicity without clear benefit after administration of PG-116800, a matrix metalloproteinase inhibitor, to patients with knee osteoarthritis: a randomized, 12-month, double-blind, placebocontrolled study. Arthritis Res Ther 2007; 9: 109. (Pubitemid 350226900)
57. Raynauld JP, Martel-Pelletier J, Bias P, et al. Protective effects of licofelone, a 5-lipoxygenase and cyclooxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first Multi- Centre Clinical Trial using quantitative MRI. Ann Rheum Dis 2009; 68(6): 938-947
58. Reginster JY, Deroisy R, Rovati LC, et al. Long-term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001; 357: 251-256 (Pubitemid 32120855)
59. Pavelká K, Gatterová J, Olejarová M, Machacek S, Giacovelli G, Rovati LC. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3-year, randomized, placebo-controlled, double-blind study. Arch Intern Med 2002; 162: 2113-2123 (Pubitemid 35168220)
60. Sawitzke AD, Shi H, Finco MF, et al. The effect of glucosamine and/or chondroitin sulfate on the progression of knee osteoarthritis: a report from the glucosamine/chondroitin arthritis intervention trial. Arthritis Rheum 2008; 58: 3183-3191
61. Dougados M, Nguyen M, Berdah L, et al. Evaluation of the structure-modifying effects of diacerein in hip osteoarthritis: ECHODIAH, a three-year, placebo-controlled trial. Evaluation of the chondromodulating effect of diacerein in OA of the hip. Arthritis Rheum 2001; 44: 2539-2547 (Pubitemid 33049332)
62. Reginster JY, Kahan A, Vignon E. A two-year prospective, randomized, double-blind, controlled study assessing the effect of chondroitin 4&6 sulfate (CS) on the structural progression of knee osteoarthritis: STOPP (STudy on Osteoarthritis Progression Prevention). Abstract ACR 2006.