Therapies for osteoarthritis today and tomorrow - review
Keywords:
Osteoarthritis, Mesenchymal stem cels, Wnt pathway, NGF antibodies
Abstract
Osteoarthritis is a common human disease with well understood pathophysiology, signs and symptoms, prevalence, risk factors, pain, and suffering with great understanding of personal, economic and social effects around the world. There are no drugs or treatments considered “disease modifying”, with symptomatic control aiming to stave off the final solution of total joint replacement. Regenerative medicine and use of mesenchymal stem cells (MSC) promised hope to change that but have so far fallen short. This review focuses on current knowledge and use of MSC in clinic, completed research, and future directions for development of this once so promising biological treatment. Powerful treatment for pain in form of monoclonal antibodies against Nerve Growth Factor (NGF) are getting close to FDA approval in the US. Wnt signalling pathway modulators that decrease inflammation, increase function and potential to regenerate cartilage should be presented to the FDA early next year.
References
References:
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27. Apfel SC. Is the therapeutic application of neurotrophic factors dead? Ann Neurol. 2002 Jan;51(1):8-11. doi: 10.1002/ana.10099.PMID: 11782976 Review. No abstract available.
28. Apfel SC. Neurotrophic factor therapy--prospects and problems. Clin Chem Lab Med. 2001 Apr;39(4):351-5. doi: 10.1515/CCLM.2001.055.29.Apfel SC. Neurotrophic factors and pain. Clin J Pain. 2000 Jun;16(2 Suppl):S7-11. doi: 10.1097/00002508-200006001-00003.
30. Eibl JK, Strasser BC, Ross GM. Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor. Neurochem Int. 2012 Dec;61(8):1266-75. doi: 0.1016/j.neuint. 2012.10.008. Epub 2012 Oct 26
31. Mitre M, Mariga A, Chao MV. Neurotrophin signalling: novel insights into mechanisms and pathophysiology. Clin Sci (Lond). 2017 Jan 1;131(1):13-23. doi: 10.1042/CS20160044
32. Tiseo PJ , Kivitz AJ , Ervin JE , Ren H , Mellis SJ. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebo-controlled exploratory study in osteoarthritis of the knee. Pain. 2014 Jul;155(7):1245-52. doi: 10.1016/j.pain.2014.03.018. Epub 2014 Mar 29
33. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip and knee. Osteoarthritis and cartilage23(2015). S8-S15
34.Dominici M, Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F, Krause D.et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315-317
35. Pittenger MF, Mackay A, Beck M, Jaiswa SCl, Douglas RK, Mosca RJ, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284: 143-147
36. Kim YS, Lee HJ, Yeo JE, Kim YI, Choi YJ, Koh YG. Isolation and characterization of human mesenchymal stem cells derived from synovial fluid in patients with osteochondral lesion of the talus. Am J Sports Med. 2015; 43: 399-406
37. de Sousa E, Casado P, Neto V, Duarte ME, Aguiar D. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem Cell Res Ther. 2014; 5: 112
38. Clevers H. Wnt/beta-Catenin signaling in development and disease. Cell. 2006; 127: 469-480
39. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008; 4: 550-556
40. Lories RJ, Corr M, Lane NE. To Wnt or not to Wnt: the bone and joint health dilemma. Nat Rev Rheumatol. 2013; 9: 328-339
41. Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009; 60: 501-512
42. Gelse K, Ekici AB, Cipa F, Swoboda B, Carl HD, Olk K, et al. Molecular differentiation between osteophytic and articular cartilage–clues for a transient and permanent chondrocyte phenotype. Osteoarthr Cartil. 2012; 20: 162-17
43. Yates KE, Shortkroff S, Reish RG. Wnt influence on chondrocyte differentiation and cartilage function. DNA Cell Biol. 2005; 24: 446-457
44. Yazici Y, McAlindon TE, Fleischmann R, Gibofsky A, Lane NE, Kivitz AJ, Skrepnik N, Armas E, Swearingen CJ, DiFrancesco A, Tambiah JRS, Hood J, Hochberg MC. A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study. Osteoarthritis Cartilage. 2017 Oct;25(10):1598-1606. doi: 10.1016/j.joca.2017.07.006. Epub 2017 Jul 13
45. Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis Cartilage. 2019 Sep;27(9):1347-1360. doi: 10.1016/j.joca.2019.05.006. Epub 2019 May 25
46. Jones D , Skrepnik N, Toselli RM, Leroy B. Incorporating Novel Mobile Health Technologies Into Management of Knee Osteoarthritis in Patients Treated With Intra-Articular Hyaluronic Acid: Rationale and Protocol of a Randomized Controlled Trial. JMIR Res Protoc. 2016 Aug 9;5(3):e164. doi: 10.2196/resprot.5940.
47. Skrepnik N , Spitzer A , Altman R , Hoekstra J , Stewart J , Toselli R. Assessing the Impact of a Novel Smartphone Application Compared With Standard Follow-Up on Mobility of Patients With Knee Osteoarthritis Following Treatment With Hylan G-F 20: A Randomized Controlled Trial. MIR Mhealth Uhealth. 2017 May 9;5(5):e64. doi: 10.2196/mhealth.7179.
1.Ling SM, Bathon JM. J Osteoarthritis in older adults. Am Geriatric Soc. 1998 Feb;46(2):216-25. doi: 10.1111/j.1532-5415. 1998. tb02543.
2. Dieppe PA, Lohmander LS. L Pathogenesis and management of pain in osteoarthritis. ancet. 2005 Mar 12-18;365(9463):965-73. doi: 10.1016/S0140-6736(05)71086-2.
3.Rice JR, Pisetsky DS. Pain in the rheumatic diseases. Practical aspects of diagnosis and treatment. Rheum Dis Clin North Am. 1999 Feb;25(1):15-30. doi: 10.1016/s0889-857x(05)70053-3
4. Murphy LB, Cisternas MG, Pasta DJ, Helmick CG, Yelin EH. Medical expenditures and earnings losses among US adults with arthritis in 2013. Arthritis Care Res (Hoboken). 2017 September 26. [Epub ahead of print]
5. United States Bone and Joint Initiative: The Burden of Musculoskeletal Diseases in the United States (BMUS), Fourth Edition. Rosemont, IL.
6. Torio CM, Moore BJ. Statistical Brief #204. National Inpatient Hospital Costs: The Most Expensive Conditions by Payer, 2013. Rockville, MD: Agency for Healthcare Research and Quality; 2016.
7. Lisa M Billesberger , Kyle M Fisher , Yawar J Qadri , Richard L Boortz-Marx. Procedural Treatments for Knee Osteoarthritis: A Review of Current Injectable Therapies. Pain Res Manag.
2020 Feb 18; 2020:3873098.
8. Juni P, Hari R, Rutjes AW, et al., “Intra-articular corticosteroid for knee osteoarthritis,” Cochrane Database Systematic Reviews, vol. 10, 2015.
9. Housman L, Arden N, Schnitzer TJ, Birbara C, Conrozier T, Skrepnik N, Wei N, Bockow B, Waddell D, Tahir H, Hammond A, Goupille P, Sanson BJ, Elkins C, Bailleul F. Intra-articular hylastan versus steroid for knee osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2014 Jul;22(7):1684-92. doi: 10.1007/s00167-013-2438-7. Epub 2013 Feb 16
10. Caplan AI. Why are MSCs therapeutic? New data: new insight. J Pathol. 2009 Jan;217(2):318-24. doi: 10.1002/path.2469
11. Jo CH, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells. 2014 May;32(5):1254-66. doi: 10.1002/stem.1634
12.Roffi A, Nakamura N, Sanchez M, Cucchiarini M, Filardo G. Injectable Systems for Intra-Articular Delivery of Mesenchymal Stromal Cells for Cartilage Treatment: A Systematic Review of Preclinical and Clinical Evidence. Int J Mol Sci. 2018 Oct 25;19(11):3322. doi: 10.3390/ijms19113322
13. Kim SH, Ha CW, Park YB, Nam E, Lee JE, Lee HJ. Intra-articular injection of mesenchymal stem cells for clinical outcomes and cartilage repair in osteoarthritis of the knee: a meta-analysis of randomized controlled trials. .Arch Orthop Trauma Surg. 2019 Jul;139(7):971-980. doi: 10.1007/s00402-019-03140-8. Epub 2019 Feb 11. PMID: 30756165 Review
14. Di Matteo B, et al. Minimally Manipulated Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Systematic Review of Clinical Evidence. Stem Cells Int. 2019. PMID: 31485234
15. Arshi A, Petrigliano FA, Williams RJ, Jones KJ. Stem Cell Treatment for Knee Articular Cartilage Defects and Osteoarthritis. Curr Rev Musculoskelet Med. 2020 Feb;13(1):20-27. doi: 10.1007/s12178-020-09598-z
16. Sipp D, Robey PG, Turner L. Clear up this stem-cell mess. Nature. 2018 Sep;561(7724):455-457. doi: 10.1038/d41586-018-06756-9
17. Sipp D, Munsie M, Sugarman J. Emerging stem cell ethics. Science. 2018 Jun 22; 360(6395): 1275. doi: 10.1126/science. Aau 4720
18. Piuzzi NS, Ng M, Chughtai M, Khlopas A, Ng K, Mont MA, Muschler GF. The Stem-Cell Market for the Treatment of Knee Osteoarthritis: A Patient Perspective.J Knee Surg. 2018 Jul;31(6):551-556. doi: 10.1055/s-0037-1604443. Epub 2017 Jul 24
19. Chu CR, Rodeo S, Bhutani N, Goodrich LR, Huard J, Irrgang J, LaPrade RF, Lattermann C, Lu Y, Mandelbaum B, Mao J, McIntyre L, Mishra A, Muschler GF, Piuzzi NS, Potter H, Spindler K, Tokish JM, Tuan R, Zaslav K, Maloney W Optimizing Clinical Use of Biologics in Orthopaedic Surgery: Consensus Recommendations From the 2018 AAOS/NIH U-13 Conference.
20. Charo RA, Sipp D. Rejuvenating Regenerative Medicine Regulation. N Engl J Med. 2018 Feb 8;378(6):504-505. doi: 10.1056/NEJMp1715736. Epub 2018 Jan 10.
21. Cyranoski D. FDA challenges stem-cell clinic. Nature. 2010 Aug 19;466(7309):909. doi: 10.1038/466909a
22. Vasiliadis AV, Galanis N. Effectiveness of AD-MSCs injections for the treatment of knee osteoarthritis: Analysis of the current literature. J Stem Cells Regen Med. 2020 May 27;16(1):3-9. doi: 10.46582/jsrm.1601002. eCollection 2020
23. Altman RD , Devji T , Bhandari M , Fierlinger A , Niazi F , Christensen R. Clinical benefit of intra-articular saline as a comparator in clinical trials of knee osteoarthritis treatments: A systematic review and meta-analysis of randomized trials. Semin Arthritis Rheum. 2016 Oct;46(2):151-159. doi: 10.1016/j.semarthrit.2016.04.003. Epub 2016 Apr 27.
24. Saltzman BM, Leroux T, Meyer MA, Basques BA, Chahal J, Bach BR Jr, Yanke AB, Cole BJ. The Therapeutic Effect of Intra-articular Normal Saline Injections for Knee Osteoarthritis: A Meta-analysis of Evidence Level 1 Studies. Am J Sports Med. 2017 Sep;45(11):2647-2653. doi: 10.1177/0363546516680607. Epub 2016 Dec 27.
25. Kopka M, Sheehan B, Degen R, Wong I, Hiemstra L, Ayeni O, Getgood A, Beavis C, Volesky M, Outerbridge R, Matache B. Arthroscopy Association of Canada Position Statement on Intra-articular Injections for Knee Osteoarthritis. Orthop J Sports Med. 2019 Jul 19;7(7): 2325967119860110. doi: 10.1177/2325967119860110. eCollection 2019 Jul.
26. Weltman JK. The 1986 Nobel Prize for Physiology or Medicine awarded for discovery of growth factors: Rita Levi-Montalcini, M.D., and Stanley Cohen, Ph.D. N Engl Reg Allergy Proc. 1987 Jan-Feb;8(1):47-8. doi: 10.2500/108854187779045385
27. Apfel SC. Is the therapeutic application of neurotrophic factors dead? Ann Neurol. 2002 Jan;51(1):8-11. doi: 10.1002/ana.10099.PMID: 11782976 Review. No abstract available.
28. Apfel SC. Neurotrophic factor therapy--prospects and problems. Clin Chem Lab Med. 2001 Apr;39(4):351-5. doi: 10.1515/CCLM.2001.055.29.Apfel SC. Neurotrophic factors and pain. Clin J Pain. 2000 Jun;16(2 Suppl):S7-11. doi: 10.1097/00002508-200006001-00003.
30. Eibl JK, Strasser BC, Ross GM. Structural, biological, and pharmacological strategies for the inhibition of nerve growth factor. Neurochem Int. 2012 Dec;61(8):1266-75. doi: 0.1016/j.neuint. 2012.10.008. Epub 2012 Oct 26
31. Mitre M, Mariga A, Chao MV. Neurotrophin signalling: novel insights into mechanisms and pathophysiology. Clin Sci (Lond). 2017 Jan 1;131(1):13-23. doi: 10.1042/CS20160044
32. Tiseo PJ , Kivitz AJ , Ervin JE , Ren H , Mellis SJ. Fasinumab (REGN475), an antibody against nerve growth factor for the treatment of pain: results from a double-blind, placebo-controlled exploratory study in osteoarthritis of the knee. Pain. 2014 Jul;155(7):1245-52. doi: 10.1016/j.pain.2014.03.018. Epub 2014 Mar 29
33. Schnitzer TJ, Marks JA. A systematic review of the efficacy and general safety of antibodies to NGF in the treatment of OA of the hip and knee. Osteoarthritis and cartilage23(2015). S8-S15
34.Dominici M, Le Blanc K., Mueller I., Slaper-Cortenbach I., Marini F, Krause D.et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8: 315-317
35. Pittenger MF, Mackay A, Beck M, Jaiswa SCl, Douglas RK, Mosca RJ, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999; 284: 143-147
36. Kim YS, Lee HJ, Yeo JE, Kim YI, Choi YJ, Koh YG. Isolation and characterization of human mesenchymal stem cells derived from synovial fluid in patients with osteochondral lesion of the talus. Am J Sports Med. 2015; 43: 399-406
37. de Sousa E, Casado P, Neto V, Duarte ME, Aguiar D. Synovial fluid and synovial membrane mesenchymal stem cells: latest discoveries and therapeutic perspectives. Stem Cell Res Ther. 2014; 5: 112
38. Clevers H. Wnt/beta-Catenin signaling in development and disease. Cell. 2006; 127: 469-480
39. Corr M. Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis. Nat Clin Pract Rheumatol. 2008; 4: 550-556
40. Lories RJ, Corr M, Lane NE. To Wnt or not to Wnt: the bone and joint health dilemma. Nat Rev Rheumatol. 2013; 9: 328-339
41. Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum. 2009; 60: 501-512
42. Gelse K, Ekici AB, Cipa F, Swoboda B, Carl HD, Olk K, et al. Molecular differentiation between osteophytic and articular cartilage–clues for a transient and permanent chondrocyte phenotype. Osteoarthr Cartil. 2012; 20: 162-17
43. Yates KE, Shortkroff S, Reish RG. Wnt influence on chondrocyte differentiation and cartilage function. DNA Cell Biol. 2005; 24: 446-457
44. Yazici Y, McAlindon TE, Fleischmann R, Gibofsky A, Lane NE, Kivitz AJ, Skrepnik N, Armas E, Swearingen CJ, DiFrancesco A, Tambiah JRS, Hood J, Hochberg MC. A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study. Osteoarthritis Cartilage. 2017 Oct;25(10):1598-1606. doi: 10.1016/j.joca.2017.07.006. Epub 2017 Jul 13
45. Deshmukh V, O'Green AL, Bossard C, Seo T, Lamangan L, Ibanez M, Ghias A, Lai C, Do L, Cho S, Cahiwat J, Chiu K, Pedraza M, Anderson S, Harris R, Dellamary L, Kc S, Barroga C, Melchior B, Tam B, Kennedy S, Tambiah J, Hood J, Yazici Y. Modulation of the Wnt pathway through inhibition of CLK2 and DYRK1A by lorecivivint as a novel, potentially disease-modifying approach for knee osteoarthritis treatment. Osteoarthritis Cartilage. 2019 Sep;27(9):1347-1360. doi: 10.1016/j.joca.2019.05.006. Epub 2019 May 25
46. Jones D , Skrepnik N, Toselli RM, Leroy B. Incorporating Novel Mobile Health Technologies Into Management of Knee Osteoarthritis in Patients Treated With Intra-Articular Hyaluronic Acid: Rationale and Protocol of a Randomized Controlled Trial. JMIR Res Protoc. 2016 Aug 9;5(3):e164. doi: 10.2196/resprot.5940.
47. Skrepnik N , Spitzer A , Altman R , Hoekstra J , Stewart J , Toselli R. Assessing the Impact of a Novel Smartphone Application Compared With Standard Follow-Up on Mobility of Patients With Knee Osteoarthritis Following Treatment With Hylan G-F 20: A Randomized Controlled Trial. MIR Mhealth Uhealth. 2017 May 9;5(5):e64. doi: 10.2196/mhealth.7179.
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2020/09/30
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