A Multicenter, Single-Blind, Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of a Cell-Mediated Gene Therapy in Degenerative Knee Arthritis Patients

Human Gene Therapy Clinical Development

Volumn 26, Issue 2, 2015, Pages 125-130

  Ha, Chul Won ^a   Cho, Jung Jong ^a   Elmallah, Randa K ^b   Cherian, Jeffrey J ^b   Kim, Tae Won ^a   Lee, Myung Chul ^a   Mont, Michael A ^b  

^a Seoul National University Hospital   (South Korea)

^b SINAI HOSPITAL OF BALTIMORE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

TRANSFORMING GROWTH FACTOR BETA1;

ARTHRALGIA; ARTICLE; CARTILAGE CELL; CARTILAGE DEGENERATION; CELL BASED GENE THERAPY; DISEASE SEVERITY; DRUG EFFICACY; DRUG SAFETY; FEMALE; FUNCTIONAL ASSESSMENT; GENETIC ENGINEERING; HUMAN; INJECTION SITE PAIN; INJECTION SITE SWELLING; INTERNATIONAL KNEE DOCUMENTATION COMMITTEE SCORE; JOINT STIFFNESS; KNEE OSTEOARTHRITIS; MALE; MULTICENTER STUDY; MUSCULOSKELETAL DISEASE; PAIN ASSESSMENT; PERIPHERAL EDEMA; PHASE 2 CLINICAL TRIAL; PHYSICAL CAPACITY; PRIORITY JOURNAL; RANGE OF MOTION; SCORING SYSTEM; SIDE EFFECT; SINGLE BLIND PROCEDURE; TREATMENT OUTCOME; VISUAL ANALOG SCALE; WESTERN ONTARIO AND MCMASTER UNIVERSITIES OSTEOARTHRITIS INDEX; AGED; CLINICAL TRIAL; CONTROLLED STUDY; GENE THERAPY; GENETICS; KNEE; MIDDLE AGED; OSTEOARTHRITIS, KNEE; PATHOLOGY; PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; TRANSPLANTATION;

AGED; CHONDROCYTES; FEMALE; GENETIC THERAPY; HUMANS; KNEE JOINT; MALE; MIDDLE AGED; OSTEOARTHRITIS, KNEE; SINGLE-BLIND METHOD; TRANSFORMING GROWTH FACTOR BETA1;

EID: 84964693329     PISSN: 23248637     EISSN: 23248645     Source Type: Journal    
DOI: 10.1089/humc.2014.145     Document Type: Article

References (21)

1. Mason JM, Breitbart AS, Barcia M, et al. Cartilage and bone regeneration using gene-enhanced tissue engineering. Clin Orthop Relat Res 2000;S171-S178.
2. Brittberg M, Lindahl A, Nilsson A, et al. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 1994;331:889-895.
3. Civinini R, Nistri L, Martini C, et al. Growth factors in the treatment of early osteoarthritis. Clin Cases Miner Bone Metab 2013;10:26-29.
4. Ha CW, Noh MJ, Choi KB, et al. Initial phase I safety of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 in degenerative arthritis patients. Cytotherapy 2012;14:247-256.
5. Langer R, Vacanti JP. Tissue engineering. Science 1993; 260:920-926.
6. Mierisch CM, Cohen SB, Jordan LC, et al. Transforming growth factor-beta in calcium alginate beads for the treatment of articular cartilage defects in the rabbit. Arthroscopy 2002;18:892-900.
7. Wang W, Rigueur D, Lyons KM. TGFbeta signaling in cartilage development and maintenance. Birth Defects Res C Embryo Today 2014;102:37-51.
8. Van Beuningen HM, Van Der Kraan PM, Arntz OJ, et al. Transforming growth factor-beta 1 stimulates articular chondrocyte proteoglycan synthesis and induces osteophyte formation in the murine knee joint. Lab Invest 1994;71:279-290.
9. Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-beta (TGF-beta). Growth Factors 1993;8:1-9.
10. Abe T, Yamada H, Nakajima H, et al. Repair of full-thickness cartilage defects using liposomal transforming growth factor-beta1. J Orthop Sci 2003;8:92-101.
11. Lee KH, Song SU, Hwang TS, et al. Regeneration of hyaline cartilage by cell-mediated gene therapy using transforming growth factor beta 1-producing fibroblasts. Hum Gene Ther 2001;12:1805-1813.
12. Song SU, Cha YD, Han JU, et al. Hyaline cartilage regeneration using mixed human chondrocytes and transforming growth factor-beta1-producing chondrocytes. Tissue Eng 2005;11:1516-1526.
13. TissueGene, Inc., Cell Technologies. Technology Overview. (Rockville, MD), 2011.
14. Wera JC, Nyland J, Ghazi C, et al. International knee documentation committee knee survey use after anterior cruciate ligament reconstruction: a 2005-2012 systematic review and world region comparison. Arthroscopy 2014;30:1505-1512.
15. Lee M, Ha C, Elmallah R, et al. A placebo-controlled, randomized trial to assess the effect of TGF-β1-expressing chondrocytes in knee arthritis patients 2015 (in press).
16. Matsumoto K, Matsunaga S, Imamura T, et al. Expression and distribution of transforming growth factor-beta and decorin during fracture healing. In Vivo 1994;8:215-219.
17. Sporn MB, Roberts AB. Peptide growth factors are multi-functional. Nature 1988;332:217-219.
18. Trippel SB. Growth factors as therapeutic agents. Instr Course Lect 1997;46:473-476.
19. Hsieh PC, Thanapipatsiri S, Anderson PC, et al. Repair of full-thickness cartilage defects in rabbit knees with free periosteal graft preincubated with transforming growth factor. Orthopedics 2003;26:393-402.
20. Bakker AC, Van De Loo FA, Van Beuningen HM, et al. Overexpression of active TGF-beta-1 in the murine knee joint: evidence for synovial-layer-dependent chondro-osteophyte formation. Osteoarthritis Cartilage 2001;9:128-136.
21. Noh MJ, Copeland RO, Yi Y, et al. Pre-clinical studies of retrovirally transduced human chondrocytes expressing transforming growth factor-beta-1 (TG-C). Cytotherapy 2010; 12:384-393.