Chemonucleolysis with chymopapain has been suggested as an alternative to surgical removal of the nucleus pulposis for degenerative disc disease. Clinical observations following the use of this enzyme have suggested that the nucleus may have the ability to regenerate. 1) We hypothesize that enzymatic dissolution of the nucleus pulposis using chymopapain or other proteoglycanase enzymes produces a reversible dissolution of the nucleus; 2) Enzymes may be available for chemonucleolysis that are equally effective as chymopapain but have less side effects in the regeneration process. In order to test these hypotheses we propose: 1) To determine the early and delayed biochemical effects of chymopapain on the intervertebral disc in experimental animals. This study will consist of both short-term and long-term evaluation of the nature of the reconstituted annulus and nucleus in terms of its microscopic appearance and biochemical composition including collagen type, proteoglycans, and matrix proteins; 2) To test alternative enzymes such as clostripain, protease K and microprotease under similar experimental conditions to determine if these enzymes act similarly to chymopapain in experimental animals in vivo, and hence whether they might be considered as possible substitutes to chymopapain for chemical dissolution of the intervertebral disc. It is anticipated that the results from these studies will have important clinical implication in the treatment of common human diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM032145-03
Application #
3152435
Study Section
Orthopedics and Musculoskeletal Study Section (ORTH)
Project Start
1983-04-01
Project End
1986-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Suguro, T; Oegema Jr, T R; Bradford, D S (1986) The effects of chymopapain on prolapsed human intervertebral disc. A clinical and correlative histochemical study. Clin Orthop Relat Res :223-31
Gotfried, Y; Bradford, D S; Oegema Jr, T R (1986) Facet joint changes after chemonucleolysis-induced disc space narrowing. Spine (Phila Pa 1976) 11:944-50
Suguro, T; Oegema Jr, T R; Bradford, D S (1986) Ultrastructural study of the short-term effects of chymopapain on the intervertebral disc. J Orthop Res 4:281-7
Persechini, A; Stull, J T; Cooke, R (1985) The effect of myosin phosphorylation on the contractile properties of skinned rabbit skeletal muscle fibers. J Biol Chem 260:7951-4