Experimental Intervertebral Discolysis

Collagenase Clostridium histolyticum for the Treatment of Peyronie's Disease: The Development of This Novel Pharmacologic Approach

“…In cases of disc‐related sciatica, the herniated nucleus pulposus compressing the nerve root was known to have a high soluble collagen content. The ability of collagenase to dissolve the collagen, liquefying the protruding nucleus and thereby relieving pressure on the nerve, was examined in a series of in vitro and animal model studies, as reviewed by Bernard Sussman and Mann [14]. Prior to collagenase, the enzyme chymopapain had been used to target the mucopolysaccharide component of the herniated nucleus.…”

“…The First Interdisciplinary Symposium on Collagenase was convened in 1970 to review research on CCH and its earliest clinical applications [13]. Among a broad range of tissue culture, in vitro, and animal model studies, researchers presented their initial work using collagenase for intervertebral discolysis, debridement of burns and dermal ulcers, and as an adjunct to cryoprostatectomy [13–17]. In particular, the application of collagenase injection to the treatment of lumbar intervertebral herniated discs was influential in the conceptual origin of collagenase as a treatment for PD.…”

“…Prior to collagenase, the enzyme chymopapain had been used to target the mucopolysaccharide component of the herniated nucleus. Unfortunately, it was associated with adverse events related to allergic reactions, necrosis due to general proteolytic activity, and effects on the annular cartilage of the disc [14]. Because purified clostridial collagenase had shown highly selective activity toward native unaltered collagen without the nonspecific proteolytic activity responsible for cartilage necrosis, it was next considered for intervertebral discolysis [14,18].…”

“…Unfortunately, it was associated with adverse events related to allergic reactions, necrosis due to general proteolytic activity, and effects on the annular cartilage of the disc [14]. Because purified clostridial collagenase had shown highly selective activity toward native unaltered collagen without the nonspecific proteolytic activity responsible for cartilage necrosis, it was next considered for intervertebral discolysis [14,18]. As was demonstrated in a double‐blind, placebo‐controlled study, intradiscal injection of collagenase showed successful resolution or reduction of pain and improved function in 12/15 (80%) patients compared with 5/15 (33%) patients receiving placebo [18].…”

Five-Year Results From Chemonucleolysis With Chymopapain or Collagenase

“…1,23,25 After successful animal experiments, collagenase (Nukleolysin) was used in a chemically purified preparation for clinical studies. 7,8,28,[67][68][69] In a double-blind study, 80% of the patients treated with collagenase showed good and excellent results, as compared with 30% in the placebo group. 9 There were no reports about allergic reactions or sensitivity to collagenase, but endplate erosions of the adjacent vertebra, mimicking the picture of discitis, were reported.…”