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.Conclusion: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.
Bibliographical noteFunding Information:
This study was supported by a grant from the National Research Foundation (NRF) in Korea, funded by the Ministry of Education, Science and Technology (2012K001412, YH), a grant of the Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120254), a grant from the Gene Therapy Project of the Ministry of Education, Science and Technology in the Republic of Korea (20110018684, JSP), and the Basic Science Research Program through a NRF grant (2012K001411, JSP). The authors also wish to thank Dr. Se Hoon Kim in the Department of Pathology (Yonsei) for his guidance in processing the specimen.
All Science Journal Classification (ASJC) codes
- Clinical Neurology