Combination of chondroitinase ABC, glial cell line-derived neurotrophic factor and Nogo A antibody delayed-release microspheres promotes the functional recovery of spinal cord injury.
Spinal cord injury (SCI) is one of the most devastating injuries for patients. Glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic factor for the regeneration of the spinal neuraxial bundle, but GDNF would degrade rapidly if the protein was injected into the site of injury; thus, it cannot exert its fullest effects. Therefore, we introduced a delivery system of GDNF, poly(lactide-co-glycolic acid) (PLGA) delayed-release microspheres, in the current study and observed the effect of PLGA-GDNF and the combination of PLGA-GDNF and another 2 agents PLGA-chondroitinase ABC (ChABC) and PLGA-Nogo A antibody in the treatment of SCI rats. Our results showed that PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres could elevate the locomotor scores of SCI rats. The effect of PLGA-GDNF was much better than that of GDNF. The cortical somatosensory evoked potential was also improved by PLGA-GDNF and the combination of chABC, GDNF, and Nogo A antibody microspheres. Our results suggest that PLGA delayed-release microsphere may be a useful and effective tool in delivering protein agents into the injury sites of patients with SCI. This novel combination therapy may provide a new idea in promoting the functional recovery of the damaged spinal cord.
From the *Department of Orthopaedics, Peking Union Medical College Hospital, Beijing; †Department of Orthopaedics, The First People's Hospital of Chengdu; and ‡Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, China.
Yu
Y
Zhang
Zuchao
Z
Gu
Guixing
G
Qiu
Yueming
Y
Song
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000494:pharmacology; D019344:Lactic Acid; D008863:Microspheres; D009043:Motor Activity / Q000187:drug effects; D009185:Myelin Proteins; D000070798:Nogo Proteins; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D000906:Antibodies; D003692:Delayed-Action Preparations; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019765:Chondroitin ABC Lyase