# Enzymatic Behavior of Condoliase in Porcine Nucleus Pulposus: Ex Vivo and In Vitro Assessment

## TL;DR

This study investigates how condoliase, an enzyme used to treat disc herniation, behaves in pig disc tissue, finding it degrades chondroitin sulfate locally without damaging collagen.

## Contribution

The study reveals condoliase's localized action in the nucleus pulposus and its lack of collagen digestion, offering new insights into its mechanism.

## Key findings

- Condoliase does not diffuse spontaneously in the nucleus pulposus but increases chondroitin sulfate digestion up to 24 hours.
- Condoliase does not degrade collagen fibers in the nucleus pulposus, preserving its structural integrity.
- The enzyme's activity peaks at 24 hours and then declines, suggesting a time-dependent pharmacological effect.

## Abstract

Condoliase is a treatment for lumbar disc herniation. This enzyme exerts its medicinal effects by digesting chondroitin sulfate (CS), which is abundant in the nucleus pulposus. However, the behavior of administered condoliase in the nucleus pulposus is not clear. Because the purpose of this study is to understand the mechanism of enzyme action, we evaluated the properties of condoliase in the nucleus pulposus.

The following were evaluated: (1) The diffusibility of fluorescein labeled condoliase injected into isolated porcine nucleus pulposus. (2) The time dependence of condoliase activity in porcine nucleus pulposus or CS solution. (3) The morphology of the enzyme‐treated nucleus pulposus tissue was characterized using scanning electron microscopy.

After injection into the nucleus pulposus, condoliase was difficult to diffuse spontaneously, and the rate of CS‐disaccharides production was significantly increased up to a peak at 24 h and decreased thereafter. Not all of the CS in the nucleus pulposus was digested by condoliase. These results suggested that condoliase digested CS locally without causing its spontaneous diffusion within the nucleus pulposus. Moreover, condoliase did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.

We demonstrated that condoliase is retained in the nucleus pulposus and exerts its pharmacological effects by locally degrading CS without degrading collagen fibers. The results obtained in this study can be useful in predicting the mechanism of the pharmacological action of condoliase in clinical practice.

Condoliase digested chondroitin sulfate locally, and did not digest the collagen fibers that form the supportive architecture of the nucleus pulposus.