Podium Presentation Osteoarthritis

23.4.10 - Evaluation of TRB-N0224, a Chemically Modified Curcumin for Treatment of Osteoarthritis

Presentation Number
23.4.10
Presentation Topic
Osteoarthritis
Lecture Time
11:42 - 11:51
Session Type
Free Papers
Corresponding Author
  • R. Nixon (Queens, US)
Authors
  • R. Nixon (Queens, US)
  • J. Coury (Manhasset, US)
  • N. Chahine (New York, US)
  • D. Grande (Manhasset, US)
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

To evaluate the effects of TRB-N0224, a chemically modified curcumin with zinc binding properties and improved pharmacokinetics, in a rabbit injury-induced model of osteoarthritis (OA).

Methods and Materials

38 skeletally mature New Zealand-like rabbits were studied in 4 groups: a sham with arthrotomy (n=6), control with ACL transection (n=6), and two treatment groups with ACL transection and administration of TRB-N0224 at low (25mg/kg/day) (n=13) and high (50mg/kg/day) (n=13) doses. After euthanization at 12 weeks, outcomes were measured by post-necropsy gross morphology, biomechanics, and cartilage and synovium histology. Rabbit blood ELISA quantified cytokine and MMP concentrations at 0, 4, 8, and 12 weeks.

Results

Both treatment groups had fewer distal femoral condyle defects than the control; the low dose demonstrated a mean 78% decrease (p<0.01). Biomechanical testing of the tibial femoral condyle revealed 1.41 MPa lower compressive strength in treatment groups than the control (p<0.05). This finding did not correlate with other tested parameters. According to the Mankin scale for OA, the low and high dose cartilage had fewer histopathological changes exhibited by lower scores (2.60 and 1.25, respectively) than the control (3.50). The control had more severe synovitis than both treatment groups. ELISA results suggested that the key mediators of OA, IL-1β, IL-6, TNFα, MMP-9, and MMP-13, decreased concentrations with TRB-N0224 treatment between weeks 4 to 12.gross picture.pngmmp figure.png

Conclusion

In pathogenesis of OA, an imbalance exists between catabolic and anabolic mediators. These results suggest the potential of TRB-N0224 to modulate MMPs and cytokines, the catabolic mediators, slowing the macroscopic and histopathological progression of OA.

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