Introduction

Condoliase is an enzyme that degrades glycosaminoglycans, specifically chondroitin sulfate (CS) of proteoglycans abundant in nucleus pulposus of intervertebral disc (IVD). Condoliase was approved as novel chemonucleolytic agent for lumbar disc herniation (LDH) by Japanese authority in 2018, and its efficacy and safety have been reported. When injected into IVD, condoliase effectively reduced intradiscal pressure and volume of herniated mass soothing compressed nerve roots without affecting surrounding nerves and vessels, because it completely lacks proteolytic activity. Its best indication is subligamentous extrusion lying beneath posterior longitudinal ligament. MRI is standard imaging modality to establish diagnosis of LDH. However, Lumbar discography is especially useful in discriminating whether LDH is subligamentous or transligamentous by depicting consistency of posterior longitudinal ligament. However, use of condoliase together with contrast media is not allowed, because there are no data on stability, efficacy and safety of condoliase when mixed with other agents. Purpose of current study is to evaluate condoliase activity when mixed with contrast media to test if these can be used together in clinical settings.

Methods

 Condoliase was mixed with two different types of iodine contrast media, ionic (amidotrizoic acid) and non-ionic (iohexol, iotrolan), under two different settings; 1) with CS, and 2) without CS. With CS, condoliase was mixed with different volumes (equal, 2x, 3x) of each contrast medium and mixture was incubated at 37^°C for 10 min. To investigate long-term effect, condoliase was mixed with equal volume of each contrast medium and mixture was incubated at 37^°C for 120 min. Without CS, condoliase was mixed with equal volume of each contrast medium without adding CS and was stored at room temperature. Condoliase activity in mixture was measured by Morgan-Elson method, in which N-acetylgalactosamine cleaved from CS by condoliase was quantified by absorbance at 585nm using spectrophotometer. The absorbance of sample without contrast medium was set as 100%.

Results 

In presence of CS, condoliase activity was maintained over 90% even after incubation with 3x volume of non-ionic media, and up to 120 min. However, equal volume of ionic medium significantly reduced condoliase activity within 10 min of incubation. In absence of CS, condoliase activity was almost completely diminished when mixed directly with ionic medium and was also reduced to 35-65% with non-ionic media.

Discussion

 Two settings; with and without CS, were used to mimic clinical scenarios, 1) condoliase was injected into IVD after discography where condoliase and contrast media coexist with CS; and 2) condoliase was mixed directly with contrast media before injection. With CS, condoliase activity was maintained by non-ionic but was reduced by ionic contrast medium. When condoliase was mixed directly without CS, both ionic and non-ionic medium reduced its activity. High inhibitory effects of ionic medium may be due to its high osmolarity, which is three to six times higher than non-ionic media. Intradiscal injection of condoliase may be feasible after establishing diagnosis of subligamentous extrusion by discography, if non-ionic iodine contrast medium were used. Condoliase should not be mixed with any type of contrast medium prior to injection.