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Selective Chemonucleolysis With Condoliase in Cynomolgus Monkeys
Dai Muramatsu1, Hiroaki Yamaguchi1, Yuka Minamisawa1
1Safety & Pharmacokinetics, Central Research Laboratory, Research & Development, Seikagaku Corporation, Higashiyamato, Tokyo, Japan.
Toxicologic Pathology
|July 8, 2020
Summary
Condoliase, an enzyme, showed less severe histopathological changes in intervertebral discs (IVDs) and vertebral bodies compared to chymopapain. These findings suggest condoliase offers a more selective approach for IVD treatment.
Area of Science:
- Biochemistry
- Histopathology
- Enzymology
Background:
- Intervertebral disc (IVD) degeneration is a significant clinical challenge.
- Enzymatic treatments are explored for IVD disorders, requiring careful evaluation of their effects.
Purpose of the Study:
- To histopathologically investigate the selective effects of condoliase, a glycosaminoglycan-degrading enzyme, in cynomolgus monkey lumbar IVDs.
- To compare the effects of condoliase with chymopapain, a proteolytic enzyme, on IVD and adjacent vertebral body (VB) tissues.
Main Methods:
- Condoliase and chymopapain were administered into the lumbar IVD of cynomolgus monkeys.
- Histopathological changes in the IVD and VB were examined from 1 to 26 weeks post-administration.
Main Results:
- Condoliase induced degenerative changes in IVD components and focal epiphyseal growth plate (EGP) disappearance, with subsequent regeneration observed.
- Vertebral body changes included bone marrow cell necrosis and new bone formation, which subsided by week 26.
- Chymopapain caused similar but more extensive and severe changes, which persisted longer than those induced by condoliase.
Conclusions:
- Condoliase demonstrated less severe and more selective histopathological changes compared to chymopapain.
- The findings suggest condoliase may offer a safer enzymatic approach for IVD treatments.
