title: Local non-viral gene delivery of apoptin delays the onset of paresis in an experimental model of intramedullary spinal cord tumor.
abstract: OBJECTIVE
  The objective of this study is to evaluate the safety and efficacy of a tumor-specific apoptosis-inducing gene, apoptin, as delivered by the non-viral carrier, PAM-RG4, in an animal model of spinal cord tumor.
  
  
  METHODS
  Male Sprague-Dawley rats were given a 2.5-μl intramedullary injection of C6 glioma (100,000) cells and randomized into three groups (day 0). On day 5, animals received a 7.5-μl intramedullary injection of Dulbecco's modified Eagle's medium (Group 1; n=7), PAM-RG4/control gene polyplex (Group 2; n=7), or PAM-RG4/apoptin gene polyplex (Group 3; n=8). Hindlimb functional strength was assessed every other day for the duration of the study. The spinal cords of killed animals were collected and hematoxylin-eosin stained.
  
  
  RESULTS
  Following treatment, animals that received apoptin had significantly higher mean functional hindlimb scores than those of sham control animals, showing a level of preserved hindlimb function throughout the study. In addition, Group 1 (sham control) and Group 2 (control gene) animals had median survival scores lower than those of animals receiving apoptin. Histopathological analysis showed marked retardation of tumor progression in apoptin-treated animals compared with sham controls.
  
  
  CONCLUSIONS
  Our study suggests that apoptin is safe for use in the mammalian spinal cord as well as effective in slowing the progression of tumor growth in the spinal cord. The significant slowing of tumor progression, as manifested by the preserved hindlimb function, coupled with the reduction in tumor volume, shows local non-viral delivery of apoptin could serve as an emerging therapy for the treatment of intramedullary spinal cord tumors.
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: W A
authors.initials: WA
authors.lastname: Pennant
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: An
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: S-J
authors.initials: SJ
authors.lastname: Gwak
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: S
authors.initials: S
authors.lastname: Choi
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: D T
authors.initials: DT
authors.lastname: Banh
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: A B L
authors.initials: AB
authors.lastname: Nguyen
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Song
authors.affiliation: Spine and Spinal Cord Institute, Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Y
authors.initials: Y
authors.lastname: Ha
authors.affiliation: Department of Chemistry, Seoul National University, Seoul, Republic of Korea.
authors.forename: J-S
authors.initials: JS
authors.lastname: Park
mesh_terms: D000818:Animals; D036022:Capsid Proteins / Q000235:genetics* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D010291:Paresis / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013120:Spinal Cord Neoplasms / Q000150:complications*
chemical_list: D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus