Chemonucleolysis for Lumbar Disc Herniation: History and Current State of the Technology

Timothy R Deer,1,* Kevin E Macadaeg,2,* Kee D Kim,3 David J Copenhaver,4 Boyle C Cheng,5 Anand Patel,6 Alexander Vaccaro,7 Kenneth D Candido,8 Pragya B Gupta,9 Douglas P Beall10 1Department of Pain Management, The Spine and Nerve Center of the Virginias, Charleston, WV, USA; 2Department of Anesthesiology and Pain Management, Indiana Spine Group, Carmel, IN, USA; 3Department of Spinal Neurosurgery, University of California, Davis, Department of Neurological Surgery, Sacramento, CA, USA; 4Department of Anesthesiology and Pain Medicine, University of California, Davis, Sacramento, CA, USA; 5Department of Neurosurgery, Allegheny Health Network Research Institute, Pittsburgh, PA, USA; 6Department of Orthopedics, Conquest Research, Winter Park, FL, USA; 7Department of Orthopaedic Surgery, Rothman Orthopaedic Institute, Philadelphia, PA, USA; 8Department of Pain Management, Chicago Anesthesia Pain Specialists, Chicago, IL, USA; 9Department of Interventional Pain Medicine, Otrimed Clinical Research, Edgewood, KY, USA; 10Department of Pain Management, Comprehensive Specialty Care, Edmond, OK, USA*These authors contributed equally to this workCorrespondence: Timothy R Deer, The Spine and Nerve Center of the Virginias, 400 Court Street, Suite 100, Charleston, WV, 25301, USA, Tel +1 304/347-6141, Fax +1 304/347-6855, Email [email protected]: The most common cause of radicular leg pain is lumbar disc herniation (LDH). LDH occurs when the central disc material, predominantly the nucleus pulposus, is displaced beyond the margins of the disc, compressing the spinal nerve roots and in turn causing radicular leg pain. Patients with persistent LDH symptoms that do not respond to conservative management have limited treatment options other than surgery. There has been a resurgence of interest in chemonucleolysis, in which an enzyme or other substance is directly injected into the intervertebral disc with the goal of reducing the size of the nucleus pulposus, relieving pressure on the nerve roots. Chemonucleolysis with chymopapain was widely used in the 1980s and 1990s as an effective treatment for LDH that was less invasive than surgery. Following the discontinuation of chymopapain in 1999, no chemonucleolytic therapy has been commercially available in the US. SI-6603 (condoliase) is a mucopolysaccharidase that selectively degrades chondroitin sulfate glycosaminoglycan (GAG) chains in the nucleus pulposus. Condoliase is approved in Japan and recently demonstrated significant improvements in worst leg pain (vs sham) in a pivotal US phase 3 clinical trial. Chemonucleolytic agents with less substrate specificity include gelified ethanol and oxygen-ozone, which are under postmarket surveillance in Europe, as well as collagenase in China. The re-emergence of chemonucleolysis is anticipated to improve the treatment landscape for LDH, providing patients with the option to avoid more invasive surgical intervention.Keywords: condoliase, SI-6603, intradiscal therapy, radicular leg pain, lumbar radiculopathy