A novel placental tissue biologic, PTP-001, inhibits inflammatory and catabolic responses in vitro and prevents pain and cartilage degeneration in a rat model of osteoarthritis

• Published in: Osteoarthritis and cartilage 2021-08, Vol.29 (8), p.1203-1212
• Main Authors: Flannery, C.R., Seaman, S.A., Buddin, K.E., Nasert, M.A., Semler, E.J., Kelley, K.L., Long, M., Favret, J., Pavesio, A., Loeser, R.F.
• Format: Article
• Language: English
• Subjects: Allograft; Amnion; Amniotic; Animals; Arthralgia - drug therapy; Biological Products - pharmacology; Cell Proliferation - drug effects; Cells, Cultured; Chondrocytes - metabolism; Chorion; Cytokines - metabolism; Disease Models, Animal; Female; Growth factor; Humans; Matrix Metalloproteinase 13 - metabolism; Osteoarthritis - drug therapy; Placenta - chemistry; Pregnancy; Rats; Synovial Membrane - cytology; Umbilical cord
• ISSN: 1063-4584; 1522-9653
• DOI: 10.1016/j.joca.2021.03.022

Characterization of a novel human placental tissue-derived biologic, PTP-001, which is in development as a candidate therapeutic for the treatment of osteoarthritis symptoms and pathophysiology. Human placental tissues from healthy donors were prepared as a particulate formulation, PTP-001. PTP-001 extracts were assayed for the presence of disease-relevant biofactors which could have beneficial effects in treating osteoarthritis. PTP-001 eluates were tested in human chondrocyte cultures to determine effects on the production of a key collagen-degrading matrix metalloproteinase, MMP-13. PTP-001 eluates were also assessed for anti-inflammatory potential in human monocyte/macrophage cultures, as well as for growth-stimulating anabolic effects in human synoviocytes. The in vivo effects of PTP-001 on joint pain and histopathology were evaluated in a rat model of osteoarthritis induced surgically by destabilization of the medial meniscus. PTP-001 was found to contain an array of beneficial growth factors, cytokines and anti-inflammatory molecules. PTP-001 eluates dose-dependently inhibited the production of chondrocyte MMP-13, and the secretion of proinflammatory cytokines from monocyte/macrophage cultures. PTP-001 eluates also promoted proliferation of cultured synovial cells. In a rat osteoarthritis model, PTP-001 significantly reduced pain responses throughout 6 weeks post-dosing. The magnitude and duration of pain reduction following a single intraarticular treatment with PTP-001 was comparable to that observed for animals treated with a corticosteroid (active control). For rats dosed twice with PTP-001, significant reductions in cartilage histopathology scores were observed. PTP-001 represents a promising biologic treatment for osteoarthritis, with a multi-modal mechanism of action that may contribute to symptom management and disease modification.